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Nanomedicine has transformed drug delivery by exploiting nanoscale properties to enhance therapeutic precision and safety. Yet, clinical translation remains hampered by issues including immune clearance, off-target distribution, and limited preclinical predictability. Bioinspired nanomedicine offers a promising solution by harnessing structural and functional features evolved in nature. Systems such as extracellular vesicles, plant-derived nanovesicles, protein- and peptide-based carriers, and biomimetic hybrids combine inherent biocompatibility with advanced capabilities in targeted delivery, barrier penetration, and immune evasion. Beyond therapeutic performance, their utilisation of biological building blocks supports reduced toxicity, scalability, and alignment with sustainable healthcare goals. This chapter reviews the rationale, design, and applications of bioinspired nanocarriers across oncology, neurology, inflammatory diseases, and nucleic acid therapeutics. It further addresses translational challenges and future opportunities at the interface of nanotechnology, precision medicine, and sustainable biomanufacturing, positioning bioinspired systems as a paradigm shift in advanced therapeutics.
School of Medicine and Population Health, University of Sheffield, Sheffield, United Kingdom
Muhamad Hawari Mansor
School of Medicine and Population Health, University of Sheffield, Sheffield, United Kingdom
Munitta Muthana
*
School of Medicine and Population Health, University of Sheffield, Sheffield, United Kingdom
*Address all correspondence to: m.muthana@sheffield.ac.uk
1. Introduction
Nanomedicine has emerged over the past three decades as a cornerstone of modern drug delivery, providing unprecedented opportunities to enhance therapeutic efficacy while minimising systemic toxicity. At its core, nanomedicine leverages the unique physicochemical properties of nanoscale materials – including high surface-to-volume ratios, tunable surface chemistry, and the capacity to traverse biological barriers – to deliver drugs, nucleic acids, and imaging agents with remarkable spatial and temporal precision [1, 2]. This approach has facilitated the development of clinically approved formulations, such as liposomal doxorubicin (DoxilⓇ), albumin-bound paclitaxel (AbraxaneⓇ), and, more recently, lipid nanoparticle (LNP)-based platforms that underpinned COVID-19 mRNA vaccines [3–5]. Despite this, broad clinical translation remains constrained by rapid clearance by the mononuclear phagocyte system, off-target biodistribution, cytotoxicity, and the limited predictive power of preclinical animal models [6, 7]. These limitations underscore the pressing need for innovative strategies capable of reconciling the theoretical promise of nanotechnology with the complexities of biological systems.
Bioinspired nanomedicine offers a compelling solution. By mimicking or directly harnessing structural and functional features of biological systems, bioinspired nanomaterials exploit mechanisms refined through millions of years of evolution, including selective transport, intercellular communication, and adaptive responses to dynamic physiological environments. Unlike many synthetic carriers, which require extensive surface modification to achieve biocompatibility [8], bioinspired systems inherit functional motifs directly from their natural templates, whether in the form of lipid membranes, protein scaffolds, or vesicular communication pathways [9].
Several classes of bioinspired nanomaterials have garnered considerable attention. Extracellular vesicles (EVs), particularly mammalian cell-derived exosomes, are naturally occurring nanocarriers enriched with proteins, lipids, and nucleic acids that mediate intercellular communication [10]. Engineered exosomes have successfully delivered chemotherapeutics [11] and small-interfering RNAs [12] across otherwise restrictive barriers, including the blood–brain barrier. Plant-derived nanovesicles (PDNs) represent another promising avenue. Sourced from edible materials such as grapefruit and ginger, these vesicles offer scalability, inherent safety, and demonstrated therapeutic efficacy in models of cancer and inflammatory bowel disease, aligning with principles of sustainability and circular bioeconomy [13, 14]. Protein- and peptide-based carriers exploit the structural precision of biomolecules to achieve controlled drug release and receptor-specific targeting. Biomimetic hybrids, such as cell membrane-coated nanoparticles and virus-like particles, combine synthetic versatility with natural functionality, facilitating immune evasion, homotypic targeting, and vaccine delivery [15, 16].
The advantages of bioinspired systems extend beyond therapeutic efficacy. By relying on biologically derived building blocks, these platforms exhibit reduced toxicity and environmental impact compared with conventional synthetic materials, supporting global initiatives for greener and more sustainable healthcare solutions [17]. Moreover, scalable production, through large-scale cell culture or extraction from agricultural by-products, positions bioinspired nanomedicine as both scientifically compelling and commercially viable.
This chapter reviews the rationale, design, and therapeutic applications of bioinspired nanocarriers – including EVs, PDNs, protein/peptide systems, and biomimetic hybrids – across oncology, neurology, inflammatory disease, and nucleic acid delivery. We also address translational hurdles and future perspectives, highlighting intersections with precision medicine, artificial intelligence, and sustainable biomanufacturing. Bioinspired nanotechnology thus emerges not only as an alternative to synthetic carriers but as a transformative paradigm bridging nature’s ingenuity with modern therapeutic demands.
The potential of bioinspired nanomedicine lies in its ability to translate evolutionarily optimised natural designs into therapeutic platforms. Over millions of years, biological systems have refined nanoscale architectures for intercellular communication, immune modulation, nutrient transport, and environmental adaptation (Figure 1). These serve as blueprints for rational nanocarrier design, offering structural and functional strategies that address the limitations of conventional synthetic systems. By studying natural templates, researchers have identified recurring design principles that inform the creation of carriers with superior efficacy, safety, and translational promise.
Figure 1.
Roadmap of bioinspired design in nanomedicine. Natural nanosystems – including exosomes, viruses and plant nanovesicles – provide evolutionary blueprints for advanced drug delivery. Their inherent properties such as structural stability, immune evasion, targeting specificity, environmental responsiveness and scalability, have been distilled into core design principles. These principles guide the engineering of next-generation carriers, including cell-derived nanocarriers, PDNs, protein- and peptide-based nanocarriers and biomimetic and hybrid systems.
2.1 Structural and functional sophistication in nature
Natural systems exemplify an extraordinary diversity of nanoscale carriers, each finely tuned through evolution to achieve stability, specificity, and efficient cargo delivery. Exosomes and other EVs encapsulate proteins, nucleic acids, and lipids within lipid bilayers, enabling navigation through complex biological fluids while preserving cargo integrity and directing uptake via surface ligands [10]. Viruses, despite their pathogenic potential, serve as archetypal nucleic acid delivery systems. Viral capsids demonstrate remarkable structural precision, protecting genomic material from degradation, evading immune detection, and exploiting host trafficking pathways to achieve highly efficient genome delivery [18]. PDNs further expand this paradigm, offering resilience under harsh gastrointestinal conditions and the capacity to transport bioactive molecules across epithelial barriers to modulate local and systemic immune responses [14, 19].
Across these systems, several recurring design principles emerge, which have informed the engineering of synthetic nanocarriers. First, structural stability is paramount: lipid bilayers, protein cages, and self-assembling scaffolds protect against enzymatic degradation and mechanical stress, enabling circulation and targeted delivery in dynamic biological environments. Second, molecular recognition is achieved through the presentation of surface proteins, glycans, or other ligands that facilitate selective binding and uptake by target cells. Third, intrinsic biodegradability ensures safe metabolism and clearance, minimising long-term accumulation and toxicity.
Integrating these design rules enables engineered carriers that replicate natural efficiency while controlling therapeutic payloads. Such systems can harmonise with endogenous transport pathways, achieve spatiotemporally controlled release, and remain amenable to scalable manufacturing – key factors for translating nanoscale innovations from bench to bedside. Moreover, these insights provide a roadmap for iterative design, where the functional motifs of natural nanocarriers guide the rational development of next-generation therapeutics that combine precision, safety, and adaptability.
2.2 Biocompatibility and immune evasion
A hallmark of natural nanocarriers is their inherent ability to evade immune detection, enabling prolonged circulation and effective targeting. Synthetic nanoparticles, by contrast, are often rapidly cleared through opsonisation and recognition by the mononuclear phagocyte system, limiting systemic exposure [20]. Exosomes and other autologous EVs are generally recognised as “self,” conferring extended circulation, diminished immunogenicity, and improved biodistribution [21]. Similarly, certain PDNs and viral particles possess surface motifs that minimise immune activation while promoting uptake, highlighting evolutionarily optimised strategies for stealth and compatibility.
Translating these principles to engineered systems has led to a suite of bioinspired immune evasion strategies. Surface camouflage, such as coating nanoparticles with red blood cell, platelet, or leukocyte membranes, displays “self” antigens that reduce clearance while retaining donor-cell functions [22, 23]. Biodegradable polymers and lipids minimise toxic by-products and inflammation, improving long-term safety. Dynamic surface engineering – modulating ligand density, charge, or conformation in response to environmental cues – further enables carriers to remain stealthy in circulation yet engage tissues at target sites [24].
Collectively, these bioinspired strategies address a critical bottleneck in nanomedicine: sustaining systemic exposure and achieving preferential accumulation without provoking adverse immune responses. Designing carriers that harmonise with host biology enhances efficacy, regulatory acceptance, and the path toward personalised therapies.
2.3 Targeting and specificity
Precise delivery of therapeutics to defined cell populations remains a central tenet of precision medicine, as off-target effects compromise efficacy and safety. Natural nanocarriers achieve remarkable specificity through ligand-receptor interactions, tissue tropism, and responsiveness to local microenvironments. Tumour-derived exosomes, for example, home to pre-metastatic niches via integrin-mediated recognition, effectively guiding their cargo to sites of disease [25]. Similarly, PDNs exhibit inherent tropism for gut-resident macrophages or epithelial cells, highlighting the potential of naturally occurring vesicles to navigate complex biological systems with remarkable fidelity [26]. Viruses also exemplify sophisticated targeting, exploiting receptor-mediated entry and intracellular trafficking to deliver genetic material with high precision.
Bioinspired engineering leverages these principles to enhance targeting. Exosomes can be genetically or chemically modified to display ligands, antibodies, or aptamers, directing them toward desired cell populations while preserving their endogenous stealth properties [27]. Protein-based carriers, including ferritin, albumin, or virus-like particles, can be engineered for receptor recognition, offering modular targeting platforms [28]. Beyond surface ligands, incorporation of stimuli-responsive materials allows carriers to respond to local cues – such as acidic pH, redox potential, or enzymatic activity – triggering site-specific release of therapeutics in diseased microenvironments [29]. These combinatorial strategies not only enhance delivery efficiency but also minimise systemic exposure, reduce off-target toxicity, and improve therapeutic indices.
The convergence of natural targeting motifs with rational engineering offers a roadmap for next-generation nanomedicines. By mimicking or integrating evolved specificity mechanisms, bioinspired carriers can achieve multi-layered targeting, combining passive biodistribution, receptor-mediated uptake, and environmentally triggered payload release. This paradigm underscores the potential of bioinspired design to refine the precision of nanotherapeutics, bridging the gap between preclinical promise and clinical translation.
2.4 Environmental responsiveness and controlled release
A hallmark of natural nanocarriers is their ability to sense and respond to environmental stimuli, enabling precise spatiotemporal control over cargo release. Viral capsids, for example, exploit pH shifts and conformational changes within endosomal compartments to release their genomes directly into the cytoplasm, achieving high-efficiency intracellular delivery while avoiding premature degradation [30]. PDNs similarly demonstrate remarkable resilience, maintaining the stability of encapsulated bioactive compounds as they transit the harsh gastrointestinal environment, yet releasing their payloads at physiologically relevant sites to modulate local or systemic responses [31]. Exosomes and EVs also exploit subtle microenvironmental signals, such as hypoxia or oxidative stress, to regulate the timing and extent of cargo release, reflecting a sophisticated integration of sense-and-response mechanisms in natural nanosystems.
Bioinspired engineering seeks to translate these adaptive strategies into synthetic carriers capable of responsive and controlled therapeutic delivery. pH-sensitive polymers and lipids enable preferential release in the acidic microenvironments characteristic of tumours or intracellular compartments, while redox-responsive linkages exploit elevated intracellular glutathione concentrations to trigger drug liberation. Enzyme-responsive materials, designed to degrade or undergo conformational shifts in the presence of matrix metalloproteinases or other disease-associated proteases, provide further layers of specificity. Such stimuli-responsive platforms not only enhance therapeutic efficacy but also reduce off-target toxicity by restricting drug activity to the desired site.
Advanced designs increasingly combine multiple environmental triggers, yielding multifunctional carriers that integrate pH, redox, and enzymatic cues to achieve hierarchical and programmable release profiles. This multi-stimuli responsiveness mirrors the dynamic adaptability of natural carriers and opens avenues for precision therapeutics in heterogeneous and complex disease microenvironments. By harnessing these principles, bioinspired nanomedicine can achieve spatiotemporally precise delivery, improving safety, efficacy, and patient outcomes, and setting a foundation for the next generation of smart drug delivery systems.
2.5 Scalability and sustainability
Beyond functional performance, natural systems offer critical insights for designing nanomedicines that are both scalable and environmentally sustainable. PDNs, for example, can be efficiently isolated from abundant agricultural by-products, including fruit peels and vegetable residues, transforming food waste into high-value therapeutic carriers and supporting a circular bioeconomy [32]. Similarly, protein-based carriers derived from casein, whey, or soy can utilise renewable agricultural streams, providing cost-effective and widely accessible raw materials while minimising reliance on petrochemical-based polymers [33].
Sustainability in bioinspired nanomedicine extends beyond sourcing; it encompasses energy-efficient and resource-conscious manufacturing processes. Emerging high-throughput production techniques, such as microfluidic synthesis, continuous-flow bioprocessing, and modular assembly, enable reproducible generation of uniform nanoparticles while reducing reagent consumption and batch-to-batch variability [34]. Integration of these technologies with renewable feedstocks provides a pathway toward large-scale production that meets clinical standards without imposing undue environmental burdens.
By marrying scalability with eco-conscious design, bioinspired nanomedicine addresses two key translational challenges: the need for reproducible, high-quality nanocarriers suitable for regulatory approval, and the imperative to reduce the environmental footprint of therapeutic manufacturing. Such approaches not only facilitate clinical translation but also exemplify a forward-looking paradigm in which innovation, efficiency, and sustainability coexist, aligning next-generation nanomedicine with both healthcare and global environmental priorities.
Bioinspired nanomedicine encompasses a wide spectrum of platforms that directly exploit or closely mimic naturally occurring nanoscale structures. These systems can broadly be categorised into four major classes: cell-derived vesicles, PDNs, protein- and peptide-based nanocarriers, and biomimetic or hybrid systems (Table 1). Each of these categories provides distinct structural advantages and therapeutic opportunities, while also presenting unique challenges for manufacturing, scalability, and clinical translation. By dissecting these platforms individually, it becomes clear how nature has guided the design of increasingly sophisticated nanocarriers that aim to address long-standing limitations in drug delivery.
Category
Size (nm)
Examples
Properties
Cell-derived nanocarriers
30–200
Exosomes, EVs, cell membrane-coated particles.
Biocompatible vesicles capable of targeted delivery and crossing the blood–brain barrier; low yield, batch heterogeneity, complex isolation.
PDNs
50–500
Grapefruit, ginger, lemon, grape vesicles.
Edible vesicles with tissue-specific uptake, orally deliverable, sustainable; uptake pathways and biodistribution are not fully understood.
Protein- and peptide-based nanocarriers
10–200
Albumin and ferritin nanoparticles, self-assembling peptides.
Structurally precise, stimuli-responsive carriers with tunable release; limited cargo size and some stability concerns.
Combines natural and synthetic features for targeted delivery and enhanced circulation; involves complex synthesis and potential immune activation.
Table 1.
Comparison of the four major categories of bioinspired nanocarriers, summarising typical size, representative examples, and key properties, including functional features, therapeutic benefits, and main limitations.
3.1 Cell-derived nanocarriers
Among the most prominent bioinspired platforms are those derived directly from mammalian cells. Exosomes and EVs represent naturally secreted nanoscale carriers (30–150 nm) that mediate intercellular communication by transferring proteins, lipids, mRNAs, and microRNAs between cells. Their inherent ability to transport molecular cargo has made them highly attractive for therapeutic delivery. Exosome-based systems offer several advantages, including excellent biocompatibility, negligible immunogenicity, and the ability to cross biological barriers. For example, exosome-encapsulated doxorubicin has demonstrated improved tumour accumulation and reduced systemic toxicity in preclinical breast cancer models [11]. Similarly, Alvarez-Erviti et al. (2011) showed that engineered exosomes could deliver siRNA across the blood–brain barrier, achieving efficient gene knockdown in neurons and glial cells following systemic administration [12] – an achievement that highlights their potential to address one of the most intractable challenges in nanomedicine.
The isolation and engineering of exosomes have been approached through several strategies, including ultracentrifugation, size-exclusion chromatography, precipitation-based kits, and, more recently, microfluidics-based platforms [35]. Drug loading can occur via passive incubation, which allows hydrophobic molecules to diffuse into vesicles, or through active methods such as electroporation, sonication, and extrusion, which transiently permeabilise vesicle membranes [36]. Advances in genetic engineering have also enabled the modification of donor cells to produce exosomes displaying specific ligands or peptides on their surface, enhancing targeting specificity [37]. Despite this promise, significant challenges remain, including low yields, batch heterogeneity, and the difficulties associated with scaling up production under GMP-compliant conditions. Moreover, their complex molecular composition complicates regulatory classification and quality control [38].
An alternative strategy within cell-derived nanocarriers involves cloaking synthetic nanoparticles with natural cell membranes, creating cell membrane-coated nanoparticles. This approach exploits the functional sophistication of biological membranes while retaining the customisable core of synthetic carriers. Red blood cell membranes, for example, can be used to shield nanoparticles from immune recognition, thereby prolonging circulation half-life [22]. Platelet membrane coatings impart adhesive and targeting properties to inflamed or injured vasculature, while cancer cell membrane cloaking allows homotypic tumour targeting via recognition of shared surface markers [39]. These systems have demonstrated utility across drug delivery, detoxification, and imaging applications, with their modularity allowing the nanoparticle core to be tailored to specific clinical needs. Nevertheless, reproducibility of membrane isolation, potential viral contamination, and risks of unintended immune activation remain major barriers to translation.
3.2 Plant-derived nanovesicles
PDNs have recently emerged as a sustainable and scalable alternative to mammalian exosomes. Derived from edible plants such as grapefruit, ginger, lemon, and oranges, PDNs typically range from 50 to 500 nm and are enriched in plant lipids, proteins, and small RNAs that can exert cross-kingdom biological effects [40]. A landmark study demonstrated that grapefruit-derived vesicles could be used to deliver chemotherapeutics to tumours in mice, enhancing therapeutic efficacy while reducing systemic toxicity compared to conventional formulations [13]. Similarly, ginger-derived nanovesicles showed anti-inflammatory activity in murine colitis models, attributed both to intrinsic phytochemicals and preferential uptake by intestinal macrophages [14]. Such findings suggest that PDNs may be particularly well-suited for oral delivery, offering a clear advantage over mammalian exosomes that generally require intravenous administration.
From a translational perspective, PDNs are appealing for several reasons: their materials, such as pectin, can be derived in high yield from abundant and inexpensive agricultural sources and food waste [41]; they are inherently safe and non-immunogenic given their edible origins; and they can be scaled efficiently, aligning with principles of green nanomedicine. These features position PDNs as a compelling bioinspired system for widespread therapeutic use. However, significant knowledge gaps remain, including an incomplete understanding of their uptake pathways, biodistribution, and long-term fate in vivo. Moreover, batch-to-batch variability and the lack of standardised isolation protocols pose challenges for reproducibility and regulatory approval. As a result, while PDNs represent one of the most promising natural vesicle platforms, they remain at an early stage of development compared to mammalian exosomes.
3.3 Protein- and peptide-based nanocarriers
Proteins and peptides have also been extensively harnessed as bioinspired nanocarriers due to their structural precision, natural abundance, and intrinsic biocompatibility. Albumin is among the most clinically validated carriers in this category. Its ability to bind hydrophobic molecules and interact with endothelial gp60 receptors has been exploited in the development of AbraxaneⓇ, an albumin-bound nanoparticle formulation of paclitaxel. This formulation enhances drug solubility and eliminates the need for toxic solvents, representing one of the earliest clinically approved nanomedicines to achieve widespread use [4].
Ferritin, a ubiquitous iron storage protein, offers another versatile platform by self-assembling into a stable 24-subunit cage with a hollow core suitable for drug or imaging agent encapsulation [42]. Its surface can be chemically or genetically modified, enabling functionalisation for tumour targeting or immune modulation. Ferritin nanoparticles have been shown to accumulate in tumours via transferrin receptor interactions and have also been investigated as platforms for vaccine development, where their highly ordered, repetitive architecture enhances antigen presentation [43, 44].
Peptide-based nanostructures provide yet another level of modularity, as short amphiphilic sequences can self-assemble into nanofibres, micelles, or hydrogels. These assemblies are responsive to environmental cues such as pH, enzymatic activity, or redox gradients, enabling precise spatiotemporal drug release [45]. Peptide-based carriers have been applied in cancer therapeutics, regenerative medicine, and tissue engineering; their biocompatibility, tunability, and ease of synthesis make them one of the most versatile and rapidly expanding classes of bioinspired nanomaterials.
3.4 Biomimetic and hybrid systems
Hybrid nanocarriers that combine natural and synthetic components represent an important frontier in bioinspired nanomedicine. Virus-like particles (VLPs) are among the most successful examples, mimicking the structural stability and immunogenicity of viruses while being rendered non-infectious by removal of their genetic material. VLP-based vaccines are already approved for hepatitis B virus (HBV) and human papillomavirus (HPV), and additional candidates are under investigation for cancer immunotherapy and emerging viral pathogens [16].
Exosome-lipid hybrids offer another innovative strategy, integrating the scalability and tunability of synthetic liposomes with the biological targeting properties of exosomes. Such systems have demonstrated enhanced toxicity against cancer cells and pH-sensitive drug release in preclinical studies, providing a promising bridge between natural and synthetic carrier platforms [46]. Other hybrid designs include polymer-protein conjugates, polysaccharide-coated nanoparticles, and synthetic polymers designed to mimic natural extracellular matrix structures, each providing unique functional advantages while expanding the design space of bioinspired nanocarriers.
Taken together, these categories illustrate the breadth of strategies employed in bioinspired nanomedicine. Exosomes and membrane-coated nanoparticles exploit mammalian biology for enhanced targeting and immune evasion; PDNs provide safe, sustainable, and orally deliverable alternatives; protein- and peptide-based carriers leverage structural precision and intrinsic biocompatibility; and hybrid platforms combine the strengths of both natural and synthetic systems. Collectively, these diverse approaches highlight the enormous potential of bioinspired nanomaterials to overcome long-standing challenges in drug delivery, setting the stage for their application in precision nanomedicine.
4. Therapeutic applications of bioinspired nanomedicine
Bioinspired nanocarriers have demonstrated therapeutic efficacy across a wide spectrum of diseases, ranging from oncology to neurological, inflammatory, and genetic disorders. Their success lies in their ability to combine the biological sophistication of natural systems with the tunability and scalability of nanotechnology, enabling precise drug delivery, enhanced stability, and reduced systemic toxicity. Unlike conventional synthetic nanoparticles, which often struggle with immune clearance and off-target effects, bioinspired systems exploit evolutionary mechanisms for cellular communication, trafficking, and immune evasion, thereby offering unique therapeutic advantages. This section highlights representative applications across major therapeutic areas, with emphasis on preclinical and emerging clinical evidence that positions bioinspired nanomedicine as a transformative paradigm in precision therapeutics.
4.1 Oncology: Precision delivery in cancer therapy
Cancer remains the most intensively studied field of application for bioinspired nanomedicine, reflecting the urgent need for tumour-specific delivery platforms that can overcome multidrug resistance, reduce systemic toxicity, and improve therapeutic efficacy. Conventional nanocarriers, such as liposomes and polymeric micelles, have achieved notable milestones in oncology, but their reliance on passive accumulation through the enhanced permeability and retention (EPR) effect has limited clinical translation due to interpatient variability and poor tumour penetration [47–49]. In contrast, bioinspired carriers leverage intrinsic tropisms, receptor-mediated uptake, and membrane-derived targeting to achieve more robust and selective tumour engagement.
4.1.1 Exosome-based cancer therapeutics
Exosomes naturally exhibit tumour tropism, a property driven by their surface repertoire of integrins, adhesion molecules, and tetraspanins such as CD9 and CD81 [50], which collectively enable preferential uptake by malignant cells. This innate homing capacity has been harnessed in therapeutic applications to improve the precision of drug delivery. For instance, dendritic cell-derived exosomes have been engineered to encapsulate chemotherapeutics like doxorubicin, showing enhanced accumulation at tumour sites and superior tumour regression compared with free drug administration in preclinical breast cancer models [11]. Similarly, mesenchymal cell-derived exosomes have been developed as carriers for RNA therapeutics, notably delivering siRNA against oncogenic KRASG12D in pancreatic cancer [51]. This approach not only produced significant tumour growth inhibition and prolonged survival in murine models but also advanced to clinical testing, where this exosome-based siRNA delivery is being evaluated in patients with metastatic pancreatic cancer (NCT03608631).
The clinical progress of such platforms highlights the unique position of exosomes at the intersection of nanomedicine and precision oncology. Their natural stability, ability to evade immune clearance, and low immunogenicity confer distinct advantages over synthetic nanoparticles. Moreover, because exosomes can be harvested from patient-derived cells, they offer the possibility of fully autologous drug delivery systems, reducing the risks of immune rejection while tailoring therapy to the molecular profile of an individual’s tumour. This patient-specific adaptability situates exosomes as frontrunners in precision medicine, where therapies are not only disease-targeted but also biologically matched to the individual, marking a paradigm shift in oncological drug delivery.
4.1.2 Plant-derived nanovesicles in oncology
PDNs are emerging as cost-effective and biocompatible alternatives to mammalian exosomes, offering advantages in scalability and safety that make them particularly attractive for translational applications. One of the most significant breakthroughs in this area was the demonstration that grapefruit-derived vesicles could encapsulate paclitaxel and achieve oral delivery in tumour-bearing mice, producing therapeutic effects comparable to intravenous administration while minimising systemic toxicity [13]. This finding not only highlighted the intrinsic stability and compatibility of PDNs but also underscored their potential to transform cancer nanomedicine by enabling patient-friendly, non-invasive dosing strategies that bypass the limitations of conventional injection-based regimens.
The versatility of PDNs has since been reinforced by vesicles derived from other plant sources. Ginger-derived nanovesicles, for example, show selective uptake by intestinal epithelial and tumour cells, pointing to unique tissue-targeting capabilities that could be harnessed for gastrointestinal malignancies [14]. This organotrophic behaviour reflects the evolutionary adaptation of plant vesicles to interact with mammalian gut cells, providing a naturally optimised delivery vehicle for oral therapies.
More recently, innovations in engineering have expanded the therapeutic potential of PDNs beyond biocompatibility and oral bioavailability. Lemon-derived nanovesicles exemplify this advance, particularly when modified with heparin-cRGD conjugation and loaded with doxorubicin (HRED) [52]. These engineered vesicles demonstrated the ability to overcome one of the most intractable challenges in oncology – drug resistance. Mechanistic studies revealed that lemon-derived vesicles engage multiple endocytic entry routes, including caveolin-mediated, clathrin-mediated, and macropinocytic uptake, enabling efficient intracellular accumulation of doxorubicin even in drug-resistant ovarian cancer cells. By broadly engaging endocytic pathways, these vesicles enhance drug retention while simultaneously disrupting ATP production, thereby limiting the energy supply required for efflux pumps such as P-glycoprotein. In preclinical models, this translated into significant tumour regression and suppression of metastatic dissemination [52], demonstrating that PDNs can not only deliver drugs effectively but also actively subvert resistance pathways that undermine conventional chemotherapies.
Together, these findings position PDNs as powerful bioinspired platforms for precision oncology. Their inherent safety, low immunogenicity, and scalability make them ideal for long-term clinical translation, while their ability to be engineered for enhanced targeting or resistance circumvention underscores their adaptability. Importantly, PDNs expand the scope of nanomedicine by combining sustainability and patient convenience with mechanistic sophistication, highlighting their potential to reshape the therapeutic landscape in cancers where conventional treatments remain inadequate.
4.2 Neurological disorders: Crossing the blood–brain barrier
Drug delivery to the brain remains one of the most formidable challenges in medicine, largely due to the highly selective permeability of the blood–brain barrier (BBB). Traditional nanocarriers often fail to achieve sufficient CNS penetration, necessitating either invasive administration routes or high systemic doses that risk toxicity. Bioinspired nanocarriers, however, offer unique opportunities by mimicking natural vesicle trafficking pathways, receptor-mediated transport, or viral tropism, thereby providing non-invasive strategies to deliver therapeutics across the BBB [53].
4.2.1 Exosome-mediated siRNA delivery in neurology
A seminal advance in exosome-based neurotherapeutics was achieved by Alvarez-Erviti et al. (2011), who engineered dendritic cell-derived exosomes to display the rabies virus glycoprotein (RVG) peptide, enabling neuron-specific delivery of siRNA across the BBB [12]. This strategy achieved robust silencing of BACE1 in murine models, a key therapeutic target in Alzheimer’s disease, providing the first proof that exosomes could be rationally programmed to deliver RNA therapeutics into the central nervous system.
Subsequent work extended this concept beyond nucleic acids to enzyme delivery. Haney et al. (2015) encapsulated catalase, a potent antioxidant, into macrophage-derived exosomes using methods such as sonication and saponin permeabilisation, achieving high loading efficiency and protection against enzymatic degradation [54]. Intranasal administration of these catalase-loaded vesicles resulted in substantial brain accumulation in Parkinson’s disease models, where they mitigated oxidative stress, reduced neuroinflammation, and preserved dopaminergic neurons.
Together, these studies highlight the translational promise of exosomes as BBB-penetrant carriers capable of stabilising fragile biomolecules and delivering them with precision. By enabling both gene silencing and enzyme replacement, exosomes are emerging as versatile platforms for tackling neurodegenerative disorders that remain refractory to conventional drug delivery systems.
4.2.2 Plant-derived nanovesicles in neurology
PDNs are increasingly recognised as promising candidates for CNS therapeutics, owing to their intrinsic biocompatibility, low immunogenicity, and ability to cross the BBB. Recent analyses have highlighted that PDNs, isolated from fruits, vegetables, and medicinal plants, can encapsulate and deliver a broad repertoire of bioactive cargos, including proteins, lipids, and nucleic acids, which reach the brain through mechanisms such as receptor-mediated transcytosis and direct membrane fusion [55]. Once internalised, these vesicles have demonstrated protective effects across a range of neurological contexts, from ischemic stroke and neuroinflammation to malignant pathologies. Their therapeutic activity appears to derive not only from their capacity to act as carriers but also from their intrinsic composition; bioactive metabolites such as gingerols, flavonoids, and alkaloids exert antioxidant, anti-inflammatory, and neuroprotective effects, supporting neuronal survival while preserving BBB integrity [55].
The dual functionality of PDNs as both natural carriers and bioactive agents highlights them as a unique alternative to synthetic nanoparticles, which often face challenges of toxicity, immunogenicity, and poor brain penetration. By leveraging the evolutionary design of plant vesicles, PDNs provide a patient-friendly, sustainable, and scalable therapeutic platform that can address delivery limitations encountered by many conventional nanomedicines. Nevertheless, despite these advantages, significant hurdles remain before clinical translation can be realised. Current isolation methods yield heterogeneous populations with variable cargo profiles, complicating reproducibility and standardisation. Moreover, drug-loading efficiency remains suboptimal, and there is a pressing need for robust engineering strategies that can integrate exogenous therapeutics without compromising vesicle stability or biological function. Addressing these challenges is essential to harness the full clinical potential of PDNs.
4.2.3 Ferritin and VLPs for neurotherapeutics
Ferritin nanocages and virus-like particles (VLPs) represent two complementary classes of bioinspired nanocarriers that are increasingly being explored for neurological applications, offering distinct yet synergistic therapeutic advantages. Ferritin, a ubiquitous iron-storage protein, has emerged as a particularly promising vehicle for CNS delivery owing to its intrinsic biocompatibility, stability, and capacity to engage transferrin receptors highly expressed on the BBB. A notable example of this approach is the encapsulation of curcumin within human heavy-chain ferritin (HFn), generating HFn-CUR nanoparticles capable of overcoming the solubility and bioavailability limitations of this anti-inflammatory and anti-amyloid compound [56]. In murine models of Alzheimer’s disease, HFn-CUR demonstrated enhanced dispersibility, efficient BBB penetration, and significant suppression of neuroinflammatory responses, including microgliosis and astrogliosis, with concomitant improvements in cognitive outcomes [56]. These findings highlight ferritin’s ability not only to facilitate the delivery of otherwise intractable molecules but also to maintain the biological integrity of neuroprotective agents in the complex environment of brain tissue.
In parallel, VLPs have gained prominence in neurological contexts where immune modulation is paramount. Their structural resemblance to native viral capsids allows for high-density antigen display, rendering them potent inducers of adaptive immune responses while avoiding the risks associated with replication-competent viruses. This property has been leveraged in the development of neuroprotective vaccines against pathogens such as the Japanese encephalitis virus and the West Nile virus, where VLP-based formulations have elicited strong, durable immunity without infection risk [57, 58]. Beyond infectious diseases, VLPs are being engineered to present self-antigens in a tolerogenic context, offering a novel route to dampen aberrant immune activity in disorders such as multiple sclerosis. While their capacity for direct BBB penetration remains limited compared to ferritin nanocages, their modularity and immunogenicity make them powerful tools for shaping systemic and peripheral immune responses that can indirectly influence CNS pathology.
Together, ferritin nanocages and VLPs embody a dual therapeutic paradigm for neurology; ferritin excels in precision delivery of small molecules and biologics directly across the BBB, whereas VLPs serve as versatile platforms for immune training and neuroprotection. Advances in both systems may enable future combinatorial strategies, integrating targeted neuroprotective delivery with tailored immunomodulation to address the multifaceted challenges posed by neurodegenerative and neuroinflammatory disorders.
4.3 Bioinspired nanocarriers in inflammatory and immune-mediated diseases
The ability of bioinspired nanocarriers to modulate immune responses has generated significant interest in treating inflammatory and immune-mediated disorders. By leveraging natural tropisms and membrane interactions, these carriers can deliver immunomodulatory agents to specific cell types and suppress inflammation.
4.3.1 Plant vesicles in inflammatory diseases
PDNs are emerging as highly adaptable mediators of immune regulation, particularly within the gastrointestinal tract. A notable example is the ability of ginger-derived vesicles to selectively target intestinal macrophages, where they suppress NLRP3 inflammasome activation and thereby alleviate colitis in preclinical models [14]. This targeted engagement of innate immune pathways illustrates how PDNs can act as precision modulators of local inflammation, rather than serving solely as passive carriers of therapeutic molecules.
What distinguishes PDNs in the context of immune-related diseases is their intrinsic capability to interact with specific immune cell populations. By delivering bioactive lipids, small RNAs, and plant-derived metabolites directly into macrophages, dendritic cells, or lymphocytes, these vesicles can reprogram inflammatory responses at the cellular level. Such effects extend beyond inflammatory bowel disease: experimental studies have shown efficacy in diverse conditions, including hepatic inflammation, systemic lupus erythematosus, and rheumatoid arthritis, highlighting their cross-tissue versatility.
Crucially, this immunomodulatory activity arises from the native molecular composition of PDNs rather than requiring extensive synthetic modification. Their membranes and cargos reflect the bioactive landscape of their plant origin, endowing them with therapeutic functionality that would otherwise need to be engineered into synthetic systems. This “built-in” immunological tuning establishes PDNs as a distinct class of nanotherapeutics, ones that leverage evolutionary design to achieve selective, cell-specific effects while minimising systemic toxicity.
4.3.2 Cell membrane-coated nanoparticles for immunomodulation
Cell membrane-coated nanoparticles represent a powerful extension of bioinspired nanomedicine, allowing synthetic cores to inherit the biological functions of their membrane source (Figure 2). In immunomodulation, this approach has proven particularly valuable, as membranes naturally present the surface proteins and receptors needed to interact with inflammatory mediators and sites of immune activity. Rather than acting solely as drug carriers, these systems can function as active decoys, neutralising pathological signals while delivering therapeutic cargo.
Figure 2.
Bioinspired nanocarriers in inflammatory and immune-mediated disease. This schematic illustrates the mechanistic and conceptual principles of two classes of bioinspired nanocarriers: PDNs and cell membrane-coated nanoparticles. (A) Ginger-derived nanovesicles are shown within the intestinal lumen interacting with epithelial cells and macrophages in the lamina propria. These PDNs deliver plant metabolites and small RNAs that suppress NLRP3 inflammasome activation in macrophages, leading to reduced secretion of inflammatory cytokines such as IL-1β and IL-18. (B) Two representative cell membrane-coated nanoparticle systems are shown within a blood vessel: macrophage membrane-coated nanoparticles (MM-NPs) and platelet membrane-coated nanoparticles (PM-NPs). MM-NPs, bearing cytokine receptors such as IL-6 R, TNFR, and CD14, act as decoys that sequester circulating inflammatory cytokines, thereby lowering systemic inflammatory burden. PM-NPs, displaying platelet adhesion molecules, target activated endothelium via binding to von Willebrand factor, collagen, and VCAM-1, enabling localised delivery of anti-inflammatory and antithrombotic drugs.
Macrophage membrane-coated nanoparticles (MM-NPs) have been shown to act as broad-spectrum “nanosponges,” sequestering pro-inflammatory cytokines such as TNF-α and IL-6, as well as bacterial endotoxins like LPS [59]. This decoy function reduces systemic hyperinflammation and improves survival in preclinical sepsis models. Unlike monoclonal antibodies that target single cytokines, MM-NPs mimic macrophages’ natural binding repertoire, providing simultaneous interception of multiple inflammatory mediators. Such versatility positions them as promising candidates for managing cytokine-driven conditions, including sepsis, viral cytokine storms, and immune-related adverse events.
Platelet membrane-coated nanoparticles (PM-NPs) extend this concept to vascular inflammation and thrombosis. By retaining adhesion molecules that recognise von Willebrand factor, collagen, and activated endothelium, PM-NPs home precisely to sites of vascular injury and thromboinflammation [60]. This targeting enables localised delivery of anti-inflammatory and antithrombotic agents, while the membrane coating itself helps compete with activated platelets, reducing clot formation and associated complications. The combination of targeted drug delivery with intrinsic biological activity highlights the dual therapeutic capacity of PM-NPs in disorders such as stroke, myocardial infarction, and atherosclerosis.
Looking forward, the integration of cell membrane-coated nanoparticles with precision medicine offers a transformative opportunity. Since cell membranes can be sourced directly from a patient’s own immune or vascular cells, the resulting nanoparticles inherit autologous surface markers, minimising immunogenicity while maximising disease-specific targeting. This opens the door to patient-tailored nanotherapeutics – for example, generating MM-NPs from individuals with sepsis to optimise cytokine neutralisation or engineering PM-NPs from patients with cardiovascular disease for enhanced vascular homing. Such approaches could yield a new class of fully personalised bioinspired nanomedicines that merge the adaptability of synthetic nanotechnology with the specificity and safety of patient-derived biology.
4.4 Gene and RNA delivery
The rapid clinical success of mRNA vaccines against COVID-19 has catalysed global interest in nucleic acid delivery platforms. While synthetic LNPs dominate current clinical applications, bioinspired carriers offer complementary advantages, including improved biocompatibility, intrinsic targeting, and potential oral administration routes.
4.4.1 Exosome-mediated RNA delivery
Exosomes are increasingly recognised as versatile carriers for RNA-based therapeutics, with applications spanning siRNA, miRNA, and mRNA delivery. Their endogenous lipid bilayer and natural tropism toward specific cell types provide a biocompatible alternative to synthetic nanoparticles or viral vectors, reducing risks of toxicity and immunogenicity while enabling efficient intracellular transfer of functional nucleic acids. Early preclinical work demonstrated that exosome formulations could deliver siRNA with high efficiency in vivo, establishing a foundation for their use as precision gene modulators [61]. More recently, this concept has expanded to encompass the delivery of complex genome-editing components such as CRISPR-Cas9, where exosomes offer a safer and potentially more controllable platform than viral systems [62].
The translational potential of exosome-mediated RNA delivery is now being tested clinically. Of particular note is a first-in-human trial (NCT05043181), which aims to investigate an exosome-based mRNA platform designed to restore low-density lipoprotein receptor (LDLR) expression in patients with homozygous familial hypercholesterolemia (HoFH). Although no results have been published yet, this therapeutic strategy exemplifies the potential of exosomes to deliver functional mRNA in a systemic disease context, addressing genetic deficiencies by facilitating the endogenous protein production pathway. The trial’s design, which assesses safety and early efficacy, reflects a shift from laboratory curiosity toward real-world application.
Together, these developments signal a broader shift in gene delivery strategies: exosomes are no longer niche laboratory tools but are evolving into translational carriers capable of safely delivering both RNA therapeutics and genome editing payloads in humans. Unlike synthetic approaches, they capitalise on evolutionary aspects of cell-to-cell communication and genetic cargo protection. If clinical outcomes are positive, exosome-mediated RNA delivery could serve as a cornerstone in precision medicine, enabling targeted, patient-tailored therapy for genetic disorders, cancers, and beyond.
4.4.2 Protein- and peptide-based carriers for nucleic acids
Protein- and peptide-based carriers are emerging as versatile RNA delivery platforms due to their modularity, tunability, and intrinsic biocompatibility. Cell-penetrating peptides and peptide amphiphiles are particularly attractive because they can self-assemble with nucleic acids through electrostatic and hydrophobic interactions, forming stable nanocomplexes that protect RNA from enzymatic degradation. Unlike synthetic polymers, these systems leverage biologically inspired motifs to enhance uptake while minimising cytotoxicity.
A key advantage of peptide carriers lies in their ability to incorporate stimuli-responsive mechanisms. Functional groups sensitive to acidic pH or intracellular redox gradients allow selective RNA release within endosomes or the cytosol, improving delivery precision. Protein-based systems extend this concept by offering intrinsic targeting and trafficking capabilities. Engineered ferritin subunits or recombinant viral proteins can be functionalised with RNA-binding domains, receptor ligands, or nuclear localisation signals, enabling subcellular precision that is difficult to achieve with lipid or exosome carriers.
Together, these carriers complement LNPs and exosomes by expanding the range of delivery strategies. Their programmable design enables disease-specific targeting and controlled intracellular trafficking, while their bioinspired architecture provides a balance of stability, low immunogenicity, and precise release. As design principles mature, protein- and peptide-based systems are poised to play an increasingly central role in advancing RNA therapeutics across cancer, genetic, and neurodegenerative disorders.
5. Translational challenges, regulatory, and manufacturing considerations
The clinical translation of bioinspired nanocarriers remains constrained by a series of biological, regulatory, and manufacturing hurdles (Figure 3). Unlike synthetic nanoparticles, which can be engineered with relative uniformity, bioinspired systems are derived from living sources and are inherently heterogeneous. Their composition is shaped by the biology of their origin and the methods of isolation, creating complexity that confers therapeutic potential but complicates reproducibility, safety evaluation, and regulatory approval. To chart a path toward clinical adoption, it is necessary to examine the major bottlenecks that impede translation.
Figure 3.
Key translational challenges of bioinspired nanocarriers. Bioinspired nanocarriers offer therapeutic promise but face major barriers to clinical translation. Five domains – biological variability, safety, manufacturing, regulatory pathways, and ethical/sustainability issues – highlight the complexity of standardisation and approval compared to synthetic systems.
Bioinspired nanocarriers are profoundly influenced by source-dependent heterogeneity. Their lipid, protein, and nucleic acid profiles vary according to the biological origin, physiological state, and processing methods. For instance, mesenchymal stem cell-derived exosomes differ substantially in cargo and immunomodulatory properties from immune cell-derived vesicles. Similarly, vesicles derived from ginger and grapefruit exhibit distinct lipid and metabolite compositions that affect biodistribution and immune interactions [13, 14]. Such diversity complicates efforts at batch-to-batch reproducibility, a prerequisite for clinical use. Even within a single donor line, vesicle yield, size distribution, and biological activity may vary. Progress in standardisation of isolation approaches, such as ultracentrifugation, size-exclusion chromatography, and tangential flow filtration (TFF), alongside potency assays, represents an essential step toward clinical translation [38].
5.1 Safety, immunogenicity, and toxicology
Although generally considered biocompatible, bioinspired nanocarriers are not inherently immunologically inert. Exosomes may activate immune pathways depending on their protein surface profile, while PDNs can introduce plant-specific glycans or metabolites with uncertain immunogenicity in humans. Protein-based systems, such as ferritin or albumin, may elicit neutralising antibodies upon repeated dosing. In parallel, the natural tropism of vesicles may result in unintended biodistribution. For instance, macrophage-derived exosomes preferentially accumulate in the liver, lungs, and pancreas, potentially limiting specific therapeutic delivery to target tissues and raising concerns about long-term toxicity [51]. Conventional toxicology paradigms, including acute, genotoxic, and reproductive toxicity assessments, may not fully capture the unique complexity of biologically derived systems. Regulatory guidance increasingly emphasises the need for case-specific evaluation, with particular attention to immunogenicity, biodistribution, and degradation kinetics.
5.2 Manufacturing and scale-up challenges
Manufacturing remains a central barrier to clinical deployment. Standard ultracentrifugation, the gold standard for exosome isolation, is laborious, low throughput, and difficult to scale. Alternatives such as TFF, chromatography, and microfluidic approaches offer potential improvements but require further optimisation to balance yield, purity, and cost-effectiveness. Beyond production, stability during storage and transport poses another challenge, as vesicles may aggregate, lose functional cargo, or degrade. Lyophilisation and cryoprotectant strategies show promise, but standardised, long-term stability conditions have yet to be established. Moreover, manufacturing under good manufacturing practice (GMP) conditions necessitates rigorous quality control, validated potency assays, and complex infrastructure. Establishing GMP-compliant production pipelines for biologically derived carriers is considerably more challenging than for synthetic liposomes, raising both cost and scalability concerns [63].
5.3 Regulatory landscape
Regulatory classification of bioinspired nanomedicines remains ambiguous. Depending on their origin and intended use, exosomes may be categorised as biologics, advanced therapy medicinal products, or drug delivery vehicles, complicating approval pathways [38]. Regulatory organisations such as the International Society for Extracellular Vesicles have called for harmonised frameworks defining potency, identity, and purity [64]. While guidelines for EVs are beginning to take shape, PDNs remain in a regulatory grey zone, with debate continuing over whether they should be considered nutraceuticals, biologics, or nanomedicines. Ongoing clinical trials, such as KRAS-targeted siRNA-loaded exosomes in pancreatic cancer (NCT03608631), exemplify both the therapeutic promise and the challenges in defining trial endpoints that capture the unique mechanisms of action of bioinspired carriers.
5.4 Ethical and sustainability considerations
Ethical sourcing of biological materials represents an additional consideration. The derivation of exosomes from stem cells or immune cells requires transparent donor consent and careful biobanking practices, particularly when allogeneic or patient-derived materials are used. In contrast, PDNs offer an environmentally sustainable alternative, as they can be produced from food waste and agricultural by-products such as citrus peels or ginger rhizomes. This approach aligns with principles of green chemistry and the circular economy, potentially reducing the environmental footprint of nanomedicine production.
Collectively, these challenges highlight the dual nature of bioinspired nanomedicine: its complexity is both its greatest strength and its central hurdle. Overcoming barriers in standardisation, safety, manufacturing, and regulation will be critical for clinical progress. Yet, the same biological sophistication that complicates translation also underpins the field’s therapeutic promise.
Bioinspired nanomedicine is entering a phase of rapid evolution, shaped by advances in biotechnology, data science, and clinical medicine, and its future will depend on simultaneously overcoming current barriers while embracing emerging opportunities (Figure 4). One of the most exciting areas of progress is the development of hybrid bio-synthetic systems that combine the natural targeting capabilities of biological carriers with the reproducibility and scalability of synthetic nanotechnology; examples such as exosome-liposome vesicles or protein-polymer conjugates help bridge the long-standing trade-off between functionality and scalability. Alongside this, next-generation targeting strategies are being designed to operate with greater precision, producing multifunctional carriers that can sense disease microenvironments, adapt their physicochemical properties, and release therapeutic cargo in a spatiotemporally controlled manner. Such systems extend beyond traditional drug delivery to actively modulate genetic and immunological pathways, with exosomes engineered to carry CRISPR-Cas9 components or tumour-targeting aptamers representing only the beginning of this transformative approach [62].
Figure 4.
Roadmap for the future of bioinspired nanomedicine. The schematic depicts the projected evolution of bioinspired nanomedicine from biologically derived carriers to AI-optimised, patient-specific therapeutics. Progression occurs through five key stages: bioinspired nanocarriers with innate targeting but limited scalability; hybrid bio-synthetic systems combining functionality and reproducibility; stimuli-responsive nanocarriers enabling adaptive drug release; AI-guided design pipelines that predict optimal formulations; and finally, precision and sustainable therapeutics integrating personalised, GMP-compliant, and ethically informed approaches. Collectively, these advances chart a translational path toward intelligent and clinically integrated nanomedicine.
A particularly powerful driver of future innovation is the integration of artificial intelligence (AI) and machine learning into the nanomedicine design pipeline. Unlike conventional trial-and-error methods, AI enables predictive modelling that can map the complex relationships between vesicle composition, biodistribution, pharmacokinetics, and therapeutic efficacy. By learning from vast multidimensional datasets – including omics profiles, patient-specific molecular signatures, and high-throughput screening results – machine learning algorithms can guide the rational design of carriers that are optimised for specific indications or even tailored to an individual patient’s biology. In practice, this could accelerate the discovery of entirely new classes of nanocarriers by rapidly testing countless virtual formulations before narrowing down to the most promising candidates for synthesis. Moreover, AI has the potential to streamline manufacturing and quality control by predicting stability, yield, and safety outcomes, reducing the bottlenecks of experimental scaling. Perhaps most importantly, AI-driven optimisation may enable a shift toward personalised medicine, where the design of therapeutic nanoparticles is not generic but adapted to the patient’s genetic, epigenetic, and immunological landscape, offering precision therapies that are both highly effective and minimally toxic. As these computational tools mature, their synergy with biotechnology and clinical data will likely redefine how nanomedicines are conceived, tested, and translated into practice.
The clinical translation of these systems will be most compelling in personalised therapies. Autologous vesicle approaches, where patient-derived exosomes are labelled with chemotherapeutics, RNA therapies, or immune modulators, exemplify the promise of reducing immunogenicity while enhancing therapeutic specificity. These strategies are particularly relevant for diseases that remain resistant to conventional therapies; the ability of bioinspired carriers to cross the BBB makes them highly attractive for treating neurodegenerative conditions, while PDNs hold unique potential for modulating the gut microbiome and addressing gastrointestinal disorders. Combination therapies are also likely to play an expanding role, with engineered exosomes capable of co-delivering siRNAs alongside checkpoint inhibitors [65], thereby making it possible to simultaneously silence oncogenic pathways and activate anti-tumour immunity in alignment with precision immunotherapy paradigms.
Nonetheless, several bottlenecks remain. Regulatory frameworks will need to adapt to ensure consistent potency assays, harmonised safety metrics, and long-term monitoring of patients. Advances in manufacturing are equally critical, with microfluidic technologies, continuous-flow systems, and modular GMP-compliant facilities expected to play a central role in enabling reproducible and scalable production. Ethical considerations, including equitable access to advanced therapies and the sustainable sourcing of biological materials, will also influence the pace and direction of development.
Taken together, these trajectories point to a future in which bioinspired nanomedicine transitions from experimental innovation to clinical mainstay. Within the coming decade, it is conceivable that exosome-based gene-editing therapies will achieve clinical approval, PDNs will be integrated into mainstream practice as sustainable carriers, and AI-optimised hybrid systems will become the cornerstone of patient-specific therapeutics. Nature continues to provide an unparalleled blueprint for addressing the challenges of drug delivery, offering biocompatibility, targeting precision, and sustainability that synthetic systems alone cannot achieve. While hurdles in standardisation, manufacturing, and regulation remain significant, the field is steadily advancing toward a paradigm shift. Bioinspired nanomedicine is not simply another technological trend but a transformative platform for personalised, precise, and sustainable therapeutics, provided that scientific innovation is matched with regulatory foresight, cross-disciplinary collaboration, and socially responsible development. If realised, this vision brings medicine closer than ever to delivering the right drug, to the right patient, at the right time.
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Written By
Lydia Williamson, Muhamad Hawari Mansor and
Munitta Muthana
Submitted: 18 September 2025Reviewed: 03 December 2025Published: 17 February 2026