bims-engexo 2026-07-19 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–07–19
eleven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered Extracellular Vesicles as Programmable Immune Interfaces: Surface and Cargo Engineering for Cancer Immunotherapy and Tolerance.
P2-engineered exosomes encapsulating curcumin alleviate cognitive decline in AD-like mice by improving microglia-related neuropathology.
Exosome-nanomaterial hybrid nanomedicine for ischemic stroke: microenvironment-informed design, therapeutic applications, and translational challenges.
Dual-engineered imDC-exosome-IKVAV nanovesicles spatiotemporally remodel the neuro-immune microenvironment for spinal cord repair.
Engineered extracellular vesicles for targeted TREX1 delivery attenuate neuroinflammation after cerebral ischemia.
Biomimetic M2 exosome-based dual-drug nanoplatform for combined immunomodulation and bone protection in rheumatoid arthritis.
Neuron-Targeted Exosomal Delivery of siRNA Against RIPK3 Slows Neurodegenerative Progression in Alzheimer's Disease.
Immunometabolic reprogramming of macrophages by miR-423-5p-enriched small extracellular vesicles delivered via glucose/ROS-responsive hydrogel for diabetic wound healing.
An E3 Aptamer-Modified T Cell-Derived Exosomal Nanoplatform for Codelivery of Astragaloside IV and PESV: Enhancing Prostate Cancer Therapy Through Immune Modulation with Implications for Clinical Translation.
Targeted co-delivery of curcumin and TRAIL via engineered extracellular vesicles: a synergistic therapy against resistant cancers.
Extracellular Vesicles, Liposomes, and Hybrid Nanovesicles: Comparative Strategies for Targeted Cancer Therapy.

Cells. 2026 Jul 03. pii: 1213. [Epub ahead of print]15(13):

Engineered Extracellular Vesicles as Programmable Immune Interfaces: Surface and Cargo Engineering for Cancer Immunotherapy and Tolerance.

Tomoyoshi Yamano, Rikinari Hanayama.

  Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that mediate intercellular communication in the immune system by transferring proteins, nucleic acids, and lipids. Their biocompatibility, nanoscale size, and capacity for cell-type-selective delivery have stimulated growing interest in engineering EVs as therapeutic platforms. In this review, we discuss recent advances in EV engineering for immune regulation, focusing on surface display, cellular targeting, and cargo loading strategies. A central concept is that engineered EVs should not be viewed simply as delivery vehicles, but as programmable immune interfaces. EVs can integrate antigen specificity, target-cell recognition, therapeutic cargo delivery, and defined immunostimulatory or tolerogenic signals within a single nanoscale particle. By combining these modular elements, engineered EVs can be designed to direct immune responses in a context-dependent manner. We examine how this principle is being applied to cancer immunotherapy, immune suppression, and antigen-specific tolerance induction, including antigen-presenting EVs, cytotoxic and RNA-loaded EVs, checkpoint-modulatory EVs, MSC-derived EVs, and engineered platforms for autoimmune and inflammatory diseases. We also discuss the clinical translation of engineered EV therapeutics, with emphasis on manufacturing, characterization, potency assays, biodistribution, safety, and regulatory challenges. Together, current advances suggest that programmable EV immune interfaces may provide a versatile foundation for next-generation cancer immunotherapy and antigen-specific immune regulation.

Keywords:  EV engineering; MSC-EV; cancer immunotherapy; cargo loading; clinical translation; extracellular vesicles; immune regulation; surface display

DOI:  https://doi.org/10.3390/cells15131213
Mater Today Bio. 2026 Aug;39 103388

P2-engineered exosomes encapsulating curcumin alleviate cognitive decline in AD-like mice by improving microglia-related neuropathology.

Xiaobin Huang, Guobo Xu, Yanhua Zhou, Dong Wang, Lili Ai, Hongmei Liu, Anran Fan, Likun Wang, Peng Zhang.

  Natural exosomes, as drug carriers, can deliver anti-inflammatory agents across the blood-brain barrier (BBB) to lesion sites in the brain, thereby demonstrating immense potential in the treatment of brain inflammation-related diseases. However, the application of natural exosomes is constrained by their poor targeting ability. Herein, we report a novel drug delivery system (P2-Exo-Cur) constructed by engineering exosomes to display the P2 peptide on their surface, thereby enabling targeted delivery of curcumin to microglia. Our results revealed that P2-Exo-Cur possesses a nanoscale membrane structure and can efficiently deliver curcumin to microglia both in vitro and in vivo. This technology provides a microglia-targeted delivery approach for anti-inflammatory agents such as curcumin, while overcoming the undesirable off-target effects that limit their efficacy. Furthermore, treatment of lipopolysaccharide (LPS)-induced inflammatory BV2 cell models with P2-Exo-Cur significantly suppressed the polarization of BV2 cells toward the M1 phenotype, as well as the secretion of pro-inflammatory cytokines. Finally, we also validated the excellent therapeutic potential of this technology in the 5xFAD mouse model. In conclusion, in this study, we for the first time constructed engineered exosomes that can specifically bind to the NCAM protein on microglia to achieve precise delivery of curcumin by expressing the P2 peptide on their surface, exerting beneficial effects in AD treatment without causing significant adverse effects. This strategy may offer a non-invasive and innovative therapeutic method for the management of brain inflammation-related diseases.

Keywords:  Alzheimer's disease; Exosomes; Microglial targeting; Neuroinflammation; P2 peptide

DOI:  https://doi.org/10.1016/j.mtbio.2026.103388
Front Cell Neurosci. 2026 ;20 1835402

Exosome-nanomaterial hybrid nanomedicine for ischemic stroke: microenvironment-informed design, therapeutic applications, and translational challenges.

Qi Zhu, Xiaodan Wu.

  Ischemic stroke (IS) remains a major cause of mortality and long-term disability despite advances in reperfusion therapy, underscoring the need for adjunctive interventions that can operate within the dynamic post-ischemic microenvironment. Exosomes and other extracellular vesicles (EVs) provide a biologically compatible interface for brain delivery, yet native vesicles are constrained by heterogeneous composition, modest loading efficiency, limited targeting control, and manufacturing variability. Exosome-nanomaterial hybrid systems are therefore emerging as modular platforms that integrate exosomal biointerfaces with the tunable payload capacity, imaging compatibility, mechanical stability, and stimulus responsiveness of synthetic nanomaterials. In this review, we propose a microenvironment-informed design paradigm for IS nanomedicine. In this framework, the ischemic lesion is not treated as a passive delivery destination, but as a staged design brief defined by blood-brain barrier (BBB) remodeling, thromboinflammation, oxidative stress, immune-cell trafficking, and neurovascular repair. We summarize how exosome source, nanomaterial component, cargo loading, surface functionalization, administration route, and characterization strategy can be selected according to these pathological cues. We further discuss therapeutic applications in BBB-penetrant delivery, neuroprotection, inflammatory modulation, imaging-guided therapy, and neurovascular recovery, together with safety, quality-control, manufacturing, and regulatory barriers. Overall, exosome-nanomaterial hybrids may become clinically meaningful for IS only when their design is microenvironment-informed, mechanism-driven, and translationally scalable.

Keywords:  blood–brain barrier; exosomes; extracellular vesicles; hybrid nanoparticles; ischemic stroke; nanomedicine; neurovascular repair; thromboinflammation

DOI:  https://doi.org/10.3389/fncel.2026.1835402
Colloids Surf B Biointerfaces. 2026 Jul 15. pii: S0927-7765(26)00570-9. [Epub ahead of print]268(Pt 1): 115982

Dual-engineered imDC-exosome-IKVAV nanovesicles spatiotemporally remodel the neuro-immune microenvironment for spinal cord repair.

Zhang Huakun, Wang Hao, Yan Rongyao.

  Spinal cord injury (SCI) leads to long-term neurological deficits, largely because secondary inflammation and poor intrinsic regeneration prevent effective tissue repair. Existing treatments, including drugs, cell transplantation, and conventional biomaterials, remain limited by insufficient efficacy, safety concerns, and weak coordination between immune regulation and neural reconstruction. Here, we developed an engineered extracellular vesicle platform by decorating immature dendritic cell-derived exosomes with the laminin-mimetic IKVAV peptide via bioorthogonal click chemistry. The resulting imDC-Exo-IKVAV preserved typical exosomal characteristics while integrating the tolerogenic features of imDC-Exo with IKVAV-mediated regenerative cues. In vitro, imDC-Exo-IKVAV reduced macrophage inflammatory activation, promoted an anti-inflammatory phenotype, and enhanced neural stem cell neuronal differentiation. After administration in SCI mice, imDC-Exo-IKVAV accumulated at the injured spinal cord and improved locomotor recovery. Mechanistically, this platform alleviated macrophage infiltration and inflammatory cytokine production, promoted M2-like polarization, enhanced axonal regeneration and remyelination, and restored electrophysiological conduction. These findings suggest that imDC-Exo-IKVAV offers a cell-free therapeutic strategy for SCI by coordinating immune microenvironment remodeling with neural repair.

Keywords:  Click chemistry; IKVAV peptide; Immature dendritic cell; Neuro-immune; Spinal cord injury

DOI:  https://doi.org/10.1016/j.colsurfb.2026.115982
J Biomed Res. 2026 Jul 25. 1-16

Engineered extracellular vesicles for targeted TREX1 delivery attenuate neuroinflammation after cerebral ischemia.

Xiaorui Lei, Xinrong Lv, Yiran Wang, Xiao Liang, Yuyao Wu, Jiangjing Yan, Liqi Zheng, Kuiyuan Hou, Tian Tian.

  Ischemic stroke stands as a principal driver of global mortality and permanent functional deficits. Notably, the clinical efficacy of current interventions is severely restricted by post-ischemic neuroinflammation. Cerebral ischemic injury prompts an inflammatory surge mediated by the cGAS-STING signaling cascade, a process initiated by the recognition of aberrantly localized cytosolic DNA. Three-prime repair exonuclease 1 (TREX1), a cytosolic DNA exonuclease, negatively regulates STING signaling; however, efficient delivery of TREX1 to the ischemic brain remains a major challenge. Here, we engineered mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) as carriers for TREX1 delivery. This was accomplished by using a palmitoylation signal-fused construct (PALM-TREX1), which enables efficient loading of the protein into extracellular vesicles. The C1C2 domains of lactadherin and the RGD-4C peptide were combined into a single recombinant fusion protein, enabling EV surface functionalization for enhanced ischemic targeting via phosphatidylserine interaction. In a mouse model of middle cerebral artery occlusion (MCAO), RGD-modified TREX1-loaded EVs (RGD-EV-TREX1) preferentially accumulated in ischemic regions, suppressed STING pathway activation, and reduced microglial activation and pro-inflammatory cytokine expression. The reduction in neuronal DNA damage and apoptosis ultimately facilitated improved neurological functional recovery, positioning RGD-EV-TREX1 as a promising cell-free therapeutic strategy for ischemic stroke.

Keywords:  TREX1; extracellular vesicles; ischemic stroke; targeted delivery

DOI:  https://doi.org/10.7555/JBR.40.20260252
Bioact Mater. 2026 Oct;64 950-965

Biomimetic M2 exosome-based dual-drug nanoplatform for combined immunomodulation and bone protection in rheumatoid arthritis.

Qing Xu, Yuan Jiang, Yi Luo, Lu Li, Bin Jiang, Cong Ren, Xiaofeng Liu, Runtong Liu, La Zhang, HongQing Liu, Yafang Chai, Yue Li, Ning Jiang, Jianwei Wang.

  The current treatment of rheumatoid arthritis (RA) remains limited by severe drug-associated side effects and poor suppression of bone erosion. Herein, we report the development of biomimetic nanoparticles (CEC NPs) that co-deliver celecoxib (CXB) and the lysine-specific demethylase 1 (LSD1) inhibitor CC-90011 via M2 macrophage-derived exosomes (M2 Exos), thereby integrating targeted delivery with innovative multi-mechanistic therapeutic strategies. The M2 Exos enable innate homing to inflamed synovium and osteoclast-rich lesions, while ensuring efficient intracellular delivery. CEC NPs combined repolarize macrophages from the M1 to M2 phenotype, suppress fibroblast-like synoviocyte activation, and critically inhibit bone erosion by blocking the LSD1-NFATc1 signaling pathway in the osteoclast. Collectively, these effects result in potent anti-inflammatory and osteoprotective outcomes. Notably, we identified CC-90011 as a previously unrecognized anti-erosive agent to directly suppress bone erosion in RA treatment. In a collagen-induced arthritis (CIA) model, CEC NPs markedly outperform monotherapies, with pronounced reduction in joint swelling, cartilage degradation, and bone erosion, without systemic toxicity. This work introduces an M2 Exo-based dual-drug delivery system as a versatile strategy for multi-mechanistic modulation of inflammation and bone destruction, offering a promising paradigm that could be extended to other inflammatory and autoimmune bone disorders.

Keywords:  Bone erosion; Fibroblast-like synoviocytes; Inflammation; Osteoclasts; Rheumatoid arthritis

DOI:  https://doi.org/10.1016/j.bioactmat.2026.05.010
Adv Sci (Weinh). 2026 Jul 11. e76558

Neuron-Targeted Exosomal Delivery of siRNA Against RIPK3 Slows Neurodegenerative Progression in Alzheimer's Disease.

Chi Zhang, Jiaqi Zhang, Yuzhi Wang, Yaodong Wang, Peng Lin, Yanling Wang, Zixuan Tang, Jintai Yu, Qin Zhou, Feiyun Cui.

  A major challenge in RNA therapeutics for central nervous system disorders is the lack of delivery systems capable of crossing the blood-brain barrier (BBB) while achieving cell-type-specific targeting. Herein, we develop an engineered exosomal siRNA delivery platform for systemic, neuron-targeted RNA transport to the brain. The platform leverages exosomes derived from an immortalized mouse hippocampal neuronal cell line as a biomimetic and functionally privileged material source, enhancing neuronal uptake and intracellular delivery efficiency. Through surface functionalization with a rabies virus glycoprotein-derived peptide, the system enables receptor-mediated BBB transcytosis and programmable siRNA loading. In human cortical organoids, the platform achieves efficient cytosolic delivery and robust gene silencing in neurons, demonstrating high delivery precision and bioavailability. As a proof of concept, targeting receptor-interacting protein kinase 3 (RIPK3) modulates necroptosis, a key pathway in inflammatory neurodegeneration. In transgenic mouse models, systemic administration suppresses RIPK3/MLKL signaling, reduces neuronal loss, and alleviates neuroinflammation and tau-associated pathology. Transcriptomic analyses further indicate stabilization of neuronal homeostasis across vulnerable brain regions. Collectively, the study establishes a modular and programmable exosomal RNA delivery platform and highlights age-defined, cell-derived biomaterials as a generalizable strategy for overcoming delivery barriers in neurological diseases.

Keywords:  RNA interference; blood–brain barrier (BBB); drug delivery; necroptosis; neuroprotection; synaptic plasticity

DOI:  https://doi.org/10.1002/advs.76558
J Nanobiotechnology. 2026 Jul 15.

Immunometabolic reprogramming of macrophages by miR-423-5p-enriched small extracellular vesicles delivered via glucose/ROS-responsive hydrogel for diabetic wound healing.

Meihua Chen, Qianru Guo, Ziyang Qin, Zihan Tang, Junjie He, Tao Xiang, Hongjuan Cui.

   BACKGROUND: Chronic diabetic wounds remain a formidable clinical challenge due to a self-sustaining immunometabolic dysfunction. The hyperglycemic and pro-oxidative microenvironment locks infiltrating macrophages in a glycolysis-dependent pro-inflammatory state, actively suppressing the phenotypic switch to pro-reparative M2 polarization and severely impairing angiogenesis. Current single-target interventions fail to disrupt this vicious inflammatory-metabolic cycle, underscoring an urgent need for strategies capable of spatiotemporally resetting local immune homeostasis.
METHOD: In this study, the pro-reparative capacity of ADSCs-EVs and UCMSCs-EVs was systematically compared through a panel of in vitro functional assays (proliferation, migration, tube formation, and macrophage polarization) and a diabetic mouse wound model. Small RNA sequencing was employed to identify a key effector miRNA enriched in UCMSCs-EVs, and its target regulatory mechanism was validated through miRNA mimic transfection combined with HDDC3 overexpression rescue experiments. Meanwhile, a glucose/ROS dual-responsive injectable hydrogel (DCH) was constructed from oxidized dextran, carboxymethyl chitosan, and phenylboronic acid-modified hyaluronic acid via physical mixing and dynamic double crosslinking through Schiff-base and boronate ester bonds, enabling the pathology-triggered, on-demand release of EVs.
RESULTS: Comparative bioactivity profiling revealed that extracellular vesicles derived from umbilical cord mesenchymal stem cells (UCMSCs-EVs) exhibited greater capacity than adipose-derived EVs to drive macrophage M2 polarization and metabolic reprogramming. Mechanistic dissection identified miR-423-5p as a highly enriched cargo within UCMSCs-EVs. This microRNA directly targeted and suppressed HDDC3 expression, thereby modulating the AMPK/mTOR signaling axis to enforce a metabolic shift from glycolysis toward fatty acid oxidation and establish a stable pro-repair phenotype. To address the poor retention and rapid clearance of free EVs within the hostile wound bed, an injectable dual-network hydrogel was engineered, integrating dynamic boronate ester and Schiff-base crosslinks. This smart platform maintained structural integrity under physiological conditions yet underwent selective dissociation exclusively in response to the elevated glucose and reactive oxygen species (ROS) levels characteristic of diabetic wounds. This pathology-triggered degradation facilitated on-demand, sustained release of UCMSCs-EVs while concurrently scavenging local ROS. The synergistic coupling of this microenvironment-responsive delivery with miR-423-5p-encoded immunometabolic regulation effectively resolved chronic inflammation and accelerated granulation tissue formation.
CONCLUSION: This study establishes a translatable framework for precision regenerative medicine by integrating stimuli-responsive biomaterial engineering with the intrinsic regulatory circuitry of stem cell-derived EVs, effectively overcoming the immunometabolic barriers inherent to diabetic tissue repair.

Keywords:  Diabetic wound repair; Glucose/ROS dual-responsive hydrogel; Immunomodulation; Macrophage metabolic reprogramming; Umbilical cord mesenchymal stem cell-derived extracellular vesicles

DOI:  https://doi.org/10.1186/s12951-026-04685-8
Int J Nanomedicine. 2026 ;21 614400

An E3 Aptamer-Modified T Cell-Derived Exosomal Nanoplatform for Codelivery of Astragaloside IV and PESV: Enhancing Prostate Cancer Therapy Through Immune Modulation with Implications for Clinical Translation.

Qing Zhang, Chenguang Liu, Sirui Wu, Nan Zhong, Junfeng Qiu, Wei Fu, Xujun You.

   Purpose: Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with current treatments often limited by drug resistance and systemic toxicity. Although traditional Chinese medicine components such as Astragaloside IV and polypeptide extract from scorpion venom (PESV) have demonstrated promising antitumor activity, their clinical translation is hampered by poor bioavailability and lack of tumor specificity. To address these limitations, we engineered an E3 aptamer-modified T cell-derived exosomal nanoplatform (EAPE) for the targeted co-delivery of Astragaloside IV and PESV in prostate cancer therapy.
Methods: EAPE was constructed and characterized, and its targeting capability, biosafety, and therapeutic performance were evaluated in vitro and in vivo. In vitro, the antitumor efficacy was assessed by proliferation, migration and apoptosis assays, while the immunomodulatory effects were investigated using a co-culture system of LNCaP cells and T lymphocytes. In vivo, the antitumor efficacy and immune activation were examined in prostate cancer xenograft mouse model, with tumor growth inhibition, apoptosis and immune responses measured.
Results: EAPE demonstrated efficient tumor-targeting capability and favorable biosafety profiles both in vitro and in vivo. EAPE demonstrated superior therapeutic efficacy against PCa by inhibiting proliferation and migration of prostate cancer cells and inducing apoptosis, while suppressing immunosuppression and activating antitumor immune response.
Conclusion: This study presents a biologically derived, targeted nanodelivery system that improves the delivery efficiency and therapeutic efficacy of Astragaloside IV and PESV. These findings support the potential of exosome-based nanoplatforms as promising strategies for enhancing the translational application of traditional Chinese medicine-derived therapeutics in prostate cancer.

Keywords:  Astragaloside IV-PESV; antitumor therapy; exosome delivery system; prostate cancer; tumor microenvironment

DOI:  https://doi.org/10.2147/IJN.S614400
Drug Deliv Transl Res. 2026 Jul 13.

Targeted co-delivery of curcumin and TRAIL via engineered extracellular vesicles: a synergistic therapy against resistant cancers.

Lang Liu, Jiahong Jiang, Zelin Wu, Xiaoli Wu, Jun Peng, Nuo Xu, Xudong Lin, Ronghui Sun, Yuyi Kang, Changhong Ke, Caijun Zhao, Qilin Huang, Fangfang Gao, Youjun Zeng, Zhengqiang Yuan.

  Renal cell carcinoma (RCC) is a resistant malignancy with a rising global incidence, thereby highlighting an urgent need for innovative treatment strategies. Curcumin (CUR), a natural polyphenolic compound, is promising for cancer treatment. However, its clinical translation has been hindered by poor bioavailability, low solubility, and rapid elimination. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-expressing extracellular vesicle (EV-T) has been proven to be an ideal platform for integrating TRAIL-sensitizing agents with TRAIL for synergistic cancer therapies. Yet, no studies have explored whether CUR could be encapsulated in EV-Ts to achieve synergistic anticancer effects. Herein we hypothesize that EV-T modified by the arginine-glycine-aspartic acid (RGD) tripeptide (denoted RGD@EV-T) exhibits enhanced tumor tropism. By loading CUR into RGD@EV-T, we could construct a novel nano-CUR formulation, namely RGD@EV-T-CUR, for co-delivery of CUR and TRAIL to achieve synergistic therapy for RCC. The RGD@EV-T was first prepared via anchoring CP05-RGD mediated integration, then CUR was efficiently encapsulated with an encapsulation rate of 53.4% to make RGD@EV-T-CUR. The RGD modification significantly enhanced the tumor tropism of EV-T by approximately 4-fold. Importantly, RGD@EV-T-CUR achieved synergistically enhanced apoptosis-inducing rate (74.9 ± 5.3%) in TRAIL-resistant RCC cells. Notably, RGD@EV-T-CUR demonstrated synergistically improved tumor growth inhibition efficacy (93.3%) compared to either CUR (28.7%) or RGD@EV-T (41.7%) monotherapy in a subcutaneous RCC xenograft tumor model in mice. The synergistic therapeutic efficacy is associated with the concurrent upregulation of death receptor 5 (DR5), downregulation of anti-apoptotic proteins, and suppression of the nuclear factor-kappaB signaling pathway. Collectively, RGD@EV-T-CUR potentially constitutes a novel cancer therapy, which is highly effective and safe for RCC treatment.

Keywords:  Composite nanodrug; Curcumin; EV-T; Synergistic efficacy; Targeted therapy

DOI:  https://doi.org/10.1007/s13346-026-02180-z
Int J Mol Sci. 2026 Jun 26. pii: 5795. [Epub ahead of print]27(13):

Extracellular Vesicles, Liposomes, and Hybrid Nanovesicles: Comparative Strategies for Targeted Cancer Therapy.

Alessia Brossa, Michela Arena, Elena Ceccotti, Enza Di Gregorio, Giuseppe Ferrauto, Benedetta Bussolati, Stefania Bruno.

  Extracellular vesicles (EVs) and liposomes are nanoscale drug delivery systems extensively investigated in oncology for their ability to improve pharmacokinetics, biodistribution, and therapeutic efficacy of anticancer agents. Liposomes are clinically validated synthetic nanocarriers characterized by high versatility, scalable production, and established regulatory approval; however, their performance is limited by tumor heterogeneity, vascular barriers, adverse effects and inefficient intracellular drug release. EVs are naturally derived nanoparticles involved in intercellular communication and exhibit intrinsic biocompatibility, low immunogenicity, and biological targeting potential; yet their translation is constrained by heterogeneity, limited loading capacity, and manufacturing challenges. Different studies indicate complementary advantages between both systems, with EVs favoring biological targeting and immune modulation and liposomes enabling controlled formulation and pharmacokinetic optimization. These features have driven the development of hybrid EV-liposome nanovesicles, which integrate synthetic and biological properties to enhance tumor targeting, therapeutic efficacy, and payload diversity, including drugs, nucleic acids, and gene-editing systems. Despite promising preclinical results, challenges remain in scalability, standardization, and mechanistic understanding of in vivo behaviour. Overall, these hybrid strategies represent a promising platform for next-generation precision nanomedicine in cancer therapy and for advancing clinical translation by addressing key limitations of current delivery systems and improving therapeutic index and patient outcomes.

Keywords:  cancer nanomedicine; drug delivery systems; tumor targeting

DOI:  https://doi.org/10.3390/ijms27135795