bims-engexo 2026-05-10 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–05–10
thirteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Exosomes as Advanced Nanocarriers: Overcoming the Blood-Brain Barrier for Targeted Therapeutic Delivery in Neurodegenerative Diseases.
Mesenchymal stem cell-derived exosome-inspired nanoformulations: a new frontier in targeted cancer therapy.
Augmenter of Liver Regeneration-Modified Adipose Mesenchymal Stem Cell-Derived Exosomes Repairs Liver Damage by Regulating Endoplasmic Reticulum Stress and Pyroptosis in a Minipig Model of Liver Injury.
AS1411-Bivalent-Cholesterol-Anchor Equipped with Zinc Phthalocya-Nine Enables NK Cells Derived Exosomes to Realize Effective Tumor-Tropism Photodynamic Therapy.
Engineered ATP-loaded extracellular vesicles: a dual-functional strategy for improving myocardial infarction therapy.
Genetically engineered extracellular vesicles-based collagen-targeting bioinspired scaffold for tendon regenerative repair.
Plant-derived nanovesicles: the intelligent nanoplatforms for therapeutics and drug delivery.
[Research progress of exosome carrying RNA in the treatment of hormone-induced osteonecrosis].
A study to investigate HLA-G targeted exosome (SOB100) in healthy subjects.
Therapeutic and Drug-Delivery Applications of Extracellular Vesicles in the Brain, Lung, and Liver.
Cell factories that manufacture microvesicles containing gene silencing RNA prodrugs.
A review of recent advances in exosome-mediated drug delivery for regenerative therapy and immunomodulation.
Oral milk exosome-PLGA nanoparticles enhance anti-tuberculosis efficacy of PBTZ169 and bedaquiline.

Curr Drug Deliv. 2026 Apr 24.

Exosomes as Advanced Nanocarriers: Overcoming the Blood-Brain Barrier for Targeted Therapeutic Delivery in Neurodegenerative Diseases.

Farhang Aliakbari, Mehregan Rahmani, Kimia Marzookian, Narges Nasrollahi Boroujeni, Alireza Alikhanian, Fahimeh Ghasemi, Daniel E Otzen, Dina Morshedi.

   INTRODUCTION: Exosomes, nanosized extracellular vesicles secreted by diverse cell types, have emerged as promising natural nanocarriers for therapeutic delivery. Their intrinsic ability to cross the Blood-Brain Barrier (BBB) positions them as valuable tools for treating neurodegenerative diseases. This review critically examines exosome biology, transport mechanisms, engineering strategies, and their clinical potential as drug-delivery platforms for the Central Nervous System (CNS).
METHODS: We analyzed recent experimental, translational, and clinical studies on exosomes and engineered derivatives, focusing on BBB penetration, therapeutic cargo delivery, and applications in brain disorders. Key advances and landmark preclinical studies were synthesized to provide a comprehensive perspective.
RESULTS: Exosomes cross the BBB through receptor-mediated transcytosis, lipid raft-associated uptake, and macropinocytosis, enabling bidirectional transport between circulation and brain. Their intrinsic cargo, including proteins, nucleic acids, and lipids, can reflect disease states and serve as predictive biomarkers. Engineered exosomes further enhance delivery potential, as surface functionalization and optimized cargo loading improve brain specificity and therapeutic efficacy in preclinical models. Collectively, both native and engineered exosomes surpass many synthetic carriers in stability, targeting, and BBB penetration.
DISCUSSION: Versus previous reviews, this manuscript integrates exosome composition, engineering, isolation technologies, and administration routes, while also addressing patent and clinical translation challenges. Importantly, it highlights quantitative and mechanistic insights into BBB transport, offering a distinct framework for advancing exosome-based CNS therapies.
CONCLUSION: Exosomes constitute a versatile platform for BBB-crossing drug delivery. By consolidating mechanistic, preclinical, and translational evidence, this review highlights their transformative potential in neurodegenerative disease therapy while outlining limitations and future directions.

Keywords:  Blood-brain barrier; central nervous system; drug delivery; exosomes; extracellular vesicles; nanocarrier; neurodegenerative diseases

DOI:  https://doi.org/10.2174/0115672018430706251211094801
Int J Pharm. 2026 May 02. pii: S0378-5173(26)00377-7. [Epub ahead of print]698 126929

Mesenchymal stem cell-derived exosome-inspired nanoformulations: a new frontier in targeted cancer therapy.

Ranjit S Jadhav, Akshada Koparde, Akshay B Kadam, Kunal Agam Kanaujia.

  Mesenchymal stem cell (MSC)-derived exosome-inspired nanoformulations have recently been proposed as an emerging approach for targeted cancer therapies, which overcome the limitations of conventional cancer therapies, such as low tumor selectivity, systemic toxicity, and the development of drug resistance. Exosomes, particularly MSC-derived exosomes, are known to offer an efficient and biocompatible approach for the targeted delivery of various therapeutic agents, including chemotherapeutic agents, to the tumor site. Here, we provide an integrative review on the unique aspects of MSC-derived exosomes (MSCEs)-inspired nanoformulations, including their tumor-targeting strategies, such as chemotaxis, receptor-mediated uptake, immune escape, and intracellular delivery, as well as their implications in cancer cell signaling. Further, the recent developments in the fabrication of bioengineering approaches for exosomes and the application of exosome-mimetic nanocarriers are also critically evaluated. In addition to therapeutic applications encompassing chemotherapy, RNA-based therapies, immunomodulation, and combination approaches, we provide a balanced discussion of the advantages, limitations, and key challenges related to large-scale production, standardization, and regulatory translation. Collectively, this review offers a unified framework bridging biological mechanisms and nanotechnological engineering, positioning MSCEs-inspired nanoformulations as next-generation platforms for precision oncology.

Keywords:  Cancer; Exosomes; Mesenchymal stem cells; Nanoformulations; Targeted therapy

DOI:  https://doi.org/10.1016/j.ijpharm.2026.126929
Antioxidants (Basel). 2026 Apr 03. pii: 450. [Epub ahead of print]15(4):

Augmenter of Liver Regeneration-Modified Adipose Mesenchymal Stem Cell-Derived Exosomes Repairs Liver Damage by Regulating Endoplasmic Reticulum Stress and Pyroptosis in a Minipig Model of Liver Injury.

Yajun Ma, Tao Liu, Lei Cao, Pujun Li, Xiangyu Lu, Yue Wang, Hongbin Wang.

  Adipose mesenchymal stem cell-derived exosomes (ADSC-Exo) have demonstrated therapeutic effects in liver diseases and injuries. The Augmenter of Liver Regeneration (ALR), a novel hepatic trophic growth factor, promotes hepatic structural and functional recovery. In this study, we constructed ALR-overexpressing ADSC-Exo (ADSC-ALR-Exo) by harnessing the messaging capacity of ADSC-Exo, and analyzed the effects of ADSC-ALR-Exo on hepatic ischemia-reperfusion injury (IRI) combined with partial hepatectomy in a minipig model. Our results indicated that, compared to the ADSC-Exo group, the ADSC-ALR-Exo group exhibited a significant reduction in reactive oxygen species (ROS) levels, alongside a notable increase in the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Furthermore, there was a marked decrease in malondialdehyde (MDA) content. Concurrently, the concentrations of pro-inflammatory factors in the blood (IL-1β, IL-18, and TNF-α) and liver tissue (IL-1β, IL-18, IL-6, and TNF-α) were significantly lower in the ADSC-ALR-Exo group, while the level of the anti-inflammatory factor IL-10 in the blood was significantly elevated. Additionally, ALR enrichment enhanced the inhibitory effect of ADSC-ALR-Exo on endoplasmic reticulum stress-related pathways, specifically ATF6, IRE1α, and PERK. Compared to ADSC-Exo, the ADSC-ALR-Exo intervention was also more effective in reducing the expression levels of NLRP3, caspase-1, and GSDMD, thereby decreasing the incidence of pyroptosis. In conclusion, ADSC-ALR-Exo mitigated liver injury by inhibiting endoplasmic reticulum stress and cellular pyroptosis induced by liver injury.

Keywords:  ADSC-ALR-Exo; endoplasmic reticulum stress; hepatic IRI; minipig; pyroptosis

DOI:  https://doi.org/10.3390/antiox15040450
Pharmaceutics. 2026 Mar 24. pii: 401. [Epub ahead of print]18(4):

AS1411-Bivalent-Cholesterol-Anchor Equipped with Zinc Phthalocya-Nine Enables NK Cells Derived Exosomes to Realize Effective Tumor-Tropism Photodynamic Therapy.

Yuchen Qi, Haoran Jiang, Yuying Zhang, Zhe Wang, Qianqian Wu, Hua Yu, Boning Xia, Jianjun Li.

  Background/Objectives: Benefiting from their outstanding tumor-penetrating ability and cytotoxic proteins and cytokines, natural-killer-cell-derived exosomes (NEX) show great potential for cell-free tumor immunotherapy. To meet the clinical tumor therapeutic need, engineered NEX are highly required to further enhance their tumor-tropism and antitumor abilities. Methods: We proposed a NEX engineering strategy, using a structure of AS1411-bivalent-cholesterol (B-Chol) anchor equipped with photosensitizer zinc phthalocyanine (ZnPc) attached on the membrane of NEX to form A-P-NEX. It not only preferably maintains the spatial structure of the AS1411 aptamer via a B-Chol anchor contributing to the tumor-tropism and stability of NEX but also significantly improves the photodynamic therapy (PDT) effect by firmly binding ZnPc in the unique G-quadruplex structure in the AS1411 aptamer. Results: The results showed that A-P-NEX could promote the precise uptake of NEX and ZnPc by tumor cells and produce obvious synergistic NEX-based immunotherapy and PDT upon laser irradiation, demonstrating excellent targeted antitumor effects both in vitro and in vivo. Conclusions: This study demonstrates a reliable NEX engineering strategy and paves the way for developing a useful tumor-tropism PDT method.

Keywords:  engineered exosome; functional nucleic acids; natural killer cell-derived exosome; photo-dynamic therapy; tumor-tropism therapy

DOI:  https://doi.org/10.3390/pharmaceutics18040401
Drug Deliv Transl Res. 2026 May 05.

Engineered ATP-loaded extracellular vesicles: a dual-functional strategy for improving myocardial infarction therapy.

Farshid Jaberi Ansari, Javad Behroozi, Mohsen Chamanara, Mostafa Shahrezaee, Ali Shakerimoghaddam, Seyed Hossein Mousavi, Amir Amanzadeh, Mohammad Ali Shokrgozar, Hossein Ahmadi Tafti, Mahdi Ghorbani, David W Greening, Reza Heidari.

  Myocardial infarction (MI) represents a major component of cardiovascular disease, primarily due to severe energy depletion in ischemic tissue. Extracellular vesicles (EVs) have recently emerged as promising cell-free nanocarriers capable of targeted delivery and intercellular communication. Leveraging these advantages, engineered EVs were investigated in this study as a direct ATP-delivery platform to cardiomyocytes. EVs were functionalized with an anti-myosin antibody to form targeted extracellular vesicles (T-EVs) and subsequently loaded with ATP, generating T-ATP-EVs for selective energy transfer to damaged myocardium. We study viability and apoptosis of ischemia cells by alamar Blue and flowcytometry (annexin-PI) under hypoxic condition in vitro also we use cardiac function, infarct size, and the expression of troponin and α-actin four weeks after MI on MI rat model in vivo for assessment cardiac repair. The results indicate that, compared with no treatment, the use of T-ATP-EVs enhances the viability of hypoxic cells by 46% and reduces apoptosis by 40%. In the animal study, T-ATP-EVs group increase 27% left ventricular ejection fraction (LVEF) also infarct size decrese 28% compared with control group. Additionally, the expression levels of troponin and α-actin increased approximately two-fold when we use T-ATP-EVs in vivo. In this study, T-ATP-EVs were investigated as a strategy to deliver ATP directly to cardiomyocytes and heart tissue . The system described here enhances cardiomyocyte survival and targeting damaged heart tissue which making a significant advancement in the treatment of MI.

Keywords:  Deliver energy; Engineered extracellular vehicles; Myocardial infarction; Targeted exreacellular vesicles; treatment of MI

DOI:  https://doi.org/10.1007/s13346-026-02143-4
Biomaterials. 2026 Apr 28. pii: S0142-9612(26)00251-6. [Epub ahead of print]334 124227

Genetically engineered extracellular vesicles-based collagen-targeting bioinspired scaffold for tendon regenerative repair.

Yan-Jing Zhang, Jing Cui, Xin-Yue Xie, Si-Si Wu, Min-Yuan Cao, Liang-Ju Ning, Xuan Li, Jie Wang, Lei-Lei Zhao, Min Zhu, Hui-Min Liu, Yi Zhang, Jing-Cong Luo, Ting-Wu Qin.

  Tendon injuries, particularly massive tendon defects, pose significant clinical challenges due to the limited regenerative capacity of tendons and suboptimal outcomes of current therapies. This study presents a bioinspired scaffold that integrates genetically engineered extracellular vesicles (EVs) with collagen-targeting capabilities into a decellularized bovine tendon sheet (DBTS) for tendon regenerative repair. Rat tendon-derived stem cells (TDSCs) were genetically modified to overexpress biglycan (Bgn) and fibromodulin (Fmod), producing bioactive EVs that drive tenogenic differentiation via the miR-145-5p/TGFβ2 signaling pathway. The incorporation of a collagen-targeting peptide (CTP) on EVs surfaces ensured efficient attachment and sustained release at the injury site. The resulting bioinspired scaffold provided a supportive microenvironment for tendon regeneration, demonstrated in vitro by improved stem cell proliferation, migration and tenogenic differentiation, and in vivo by enhanced collagen alignment, extracellular matrix remodeling, and biomechanical performance of regenerated Achilles tendons in rats. This scaffold represents an innovative approach in cell-free regenerative strategy, offering targeted modulation of the tendon niche with translational potential for treating massive tendon injuries.

Keywords:  Biglycan; Bioinspired scaffold; Collagen-targeting; Dual-engineered extracellular vesicles; Fibromodulin; Tendon regeneration

DOI:  https://doi.org/10.1016/j.biomaterials.2026.124227
J Nanobiotechnology. 2026 May 02.

Plant-derived nanovesicles: the intelligent nanoplatforms for therapeutics and drug delivery.

Shuang Du, Dan Jia, Guohui Liang, Yonghui Dou.

  Extracellular vesicles (EVs) are cell-secreted phospholipid bilayer vesicles that play a key role in intercellular communication by transporting molecular cargo and engaging in surface-level signaling. Due to their intrinsic biological features, EVs not only reflect the functional attributes of their originating cells but also hold promise as both therapeutic agent and natural carriers for targeted delivery. In recent years, plant-derived nanovesicles (PDNVs) containing bioactive molecules have attracted the attention of researchers because of their better biocompatibility, low immunogenicity, wide range of sources, and ability to act as natural therapeutic agents for diseases. PDNVs play an increasingly important role in human-plant interactions, as they are able to enter the human system and deliver effector molecules to cells, which in turn modulate cellular signaling pathways. PDNVs play a critical role in human health and disease. This review provides a comprehensive overview of PDNVs, encompassing their biogenesis, methods of isolation and purification, physicochemical characterization, stability, and storage strategies. It further explores their routes of administration, internalization, and biodistribution as therapeutic agents, highlighting their potential in the treatment of conditions such as inflammation, cancer, tissue regeneration, viral infections, liver and brain disorders, and osteoporosis. Lastly, the review examines current clinical applications of PDNVs and the key challenges hindering their broader implementation. We look forward to further exploration of the functions of PDNVs to facilitate their clinical translation and increase their benefits in humans.

Keywords:  Clinical application; Drug delivery; Engineering modification; Plant-derived nanovesicles; Therapeutic potential

DOI:  https://doi.org/10.1186/s12951-026-04484-1
Zhongguo Gu Shang. 2026 Apr 25. 39(4): 426-32

[Research progress of exosome carrying RNA in the treatment of hormone-induced osteonecrosis].

Yue Meng, Rui Bao, Dongyu Shang, Xilin Xu, Dawei Zhang, Yichang Jiang.

  Osteonecrosis is a metabolic disease commonly induced by glucocorticoid administration, which impedes the blood supply to bone, promotes osteocyte death, and subsequently leads to alterations in bone structure and collapse of the femoral head. Key molecular mechanisms include osteocyte apoptosis, dysregulated autophagy, oxidative stress, and vascular endothelial dysfunction, among others. Although progress has been made in understanding the pathogenesis of steroid-induced osteonecrosis, the development of effective preventive and therapeutic strategies remains an ongoing challenge. Exosomes are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication. Their unique cargo capacity enables them to transport bioactive molecules, including ribonucleic acid (RNA), between cells. Increasing evidence suggests that RNA-loaded exosomes exert dual therapeutic effects:directly promoting osteogenesis and angiogenesis, and modulating pathological processes via the delivery of regulatory RNAs. These properties indicate that exosomes hold immense potential for targeted intervention and therapy in osteonecrosis.

Keywords:  Angiogenesis; Exosome; Osteonecrosis; Oxidative stress; Ribonucleic acid

DOI:  https://doi.org/10.12200/j.issn.1003-0034.20250363
Nanomedicine (Lond). 2026 May 05. 1-6

A study to investigate HLA-G targeted exosome (SOB100) in healthy subjects.

Kai-Jie Yang, Ni-Yen Yu, Ronald Goldwater, Chi-Hao Chang, Chia-Mei Liu, Kai-Wen Kan, Yi-Wen Chen, Der-Yang Cho, David Melville, Jennifer Hui-Chun Ho.

  To investigate the safety profile and tolerability of SOB100, a targeted exosome drug delivery platform derived from HEK293T cells engineered with an anti-Human Leukocyte Antigen G(HLA-G) nanobody. An open-label, dose-escalation Phase I with a total of fifteen subjects will be enrolled in five cohorts, three subjects in each cohort, comprising one single-ascending dose (SAD) cohort or multiple-ascending dose (MAD) cohorts (low, medium, and high dose levels). This will be the first in-human study to evaluate the safety and tolerability of HLA-G targeted exosome (SOB100) in healthy volunteers.Trial registration number: NCT07219940 (ClinicalTrials.gov).

Keywords:  Exosome; HLA-G; SOB100; clinical trial protocol; drug delivery platform; phase 1

DOI:  https://doi.org/10.1080/17435889.2026.2668706
Curr Drug Deliv. 2026 Apr 28.

Therapeutic and Drug-Delivery Applications of Extracellular Vesicles in the Brain, Lung, and Liver.

Rokgi Hong, Budjav Jadamba, Gyeongmin Jeong, Younghoon Jang, Jun Go, Heedoo Lee.

  Extracellular vesicles (EVs), encompassing exosomes, microvesicles, and apoptotic bodies, are pivotal mediators of intercellular communication, facilitating the transfer of nucleic acids, proteins, and lipids between cells and thereby influencing a wide range of physiological and pathological processes. Their inherent biocompatibility, nanoscale size, and ability to reflect the molecular signatures of their parental cells have positioned EVs as promising therapeutic agents for various diseases, including neurological, cardiovascular, hepatic, and pulmonary disorders, for which conventional therapies often provide limited or nonspecific benefits. Notably, EVs can traverse biological barriers such as the blood-brain barrier, enhancing their clinical applicability by enabling drug delivery to anatomically protected sites. Furthermore, patient-derived EVs exhibit distinct molecular profiles compared with healthy controls, underscoring their potential as diagnostic biomarkers and modulators of disease pathogenesis, with growing evidence demonstrating their ability to distinguish disease subtypes, predict prognosis, and monitor therapeutic responses. Accumulating evidence also indicates that EVs regulate immune responses, angiogenesis, and tissue remodeling, thereby contributing to both physiological homeostasis and pathological processes. Engineered EVs further offer innovative drug delivery solutions by improving therapeutic precision while minimizing adverse effects associated with conventional systems, and they hold considerable promise for future personalized- medicine strategies. This review summarizes current knowledge on the diverse roles of EVs across major organ diseases, highlights their translational potential as both therapeutic agents and biomarkers, and discusses emerging challenges that must be addressed for successful clinical translation. By providing a comprehensive overview, this study aims to advance the clinical translation of EVs in precision medicine.

Keywords:  Extracellular vesicles; biomarkers; diagnostics; drug delivery; pathogenesis; therapeutics

DOI:  https://doi.org/10.2174/0115672018418913251206062505
PNAS Nexus. 2026 May;5(5): pgag121

Cell factories that manufacture microvesicles containing gene silencing RNA prodrugs.

Yanan Feng, Weijing Xu, Ning Deng, Jing Jin, Xiaohong Tang, Jaishree Garhyan, Stanley N Cohen.

  Among the vehicles investigated as delivery agents for antisense RNAs are extracellular vesicles (EVs) released from cultured cells. Arrestin domain-containing 1 (ARRDC1)-mediated microvesicles (ARMMs) are naturally occurring EVs that uniquely are formed by outward budding of cytoplasmic membranes. Previous work has shown that ARMMs production is quantitatively controlled by the ARRDC1 protein and that ARRDC1 and macromolecules attached to it are loaded into nascent ARMMs during ARMM formation. Here, we report a strategy for constructing cell factories that biologically manufacture both ARMMs and short hairpin RNA (shRNA)-like antisense RNA precursors, designated as shT-RNAs. Human HEK293T cells mutated in the endoribonuclease DICER1 were engineered to express a fusion protein containing components of ARRDC1 and the trans-activator of transcription (Tat) peptide encoded by the HIV-1 virus. Prodrug RNAs were constructed by replacing the canonical loop regions of shRNAs with a 24-nucleotide segment derived from the Tat-binding trans-activation response (TAR) element. We show that a truncated TAR sequence embedded within the structural framework of shT-RNAs enables their linkage to the ARRDC1-Tat fusion protein and consequent loading of the RNAs into nascent ARMMs, and that RNA is protected by ARMMs membranes from attack by external ribonucleases. We further show that prodrug modules consisting of shT-RNAs that target different genomic sequences of SARS-CoV-2 virus and are manufactured as components of a single transcript can, when delivered by ARMMs, be activated to suppress virus RNA production. Our results indicate that the ARMMs-based platform we have designed can deliver gene-silencing RNAs in the form of biologically produced shRNA-like prodrugs.

Keywords:  ARMMs; SARS-CoV-2; antisense; extracellular vesicles; shRNA

DOI:  https://doi.org/10.1093/pnasnexus/pgag121
Biomed Eng Online. 2026 May 04.

A review of recent advances in exosome-mediated drug delivery for regenerative therapy and immunomodulation.

Mohammad Asim Azhar, Eman Alshehri, Abdullah M Assiri, Dieter C Broering, Ahmed Yaqinuddin, Tanveer Ahmad Mir.

  Exosomes are small, nanoscale extracellular vesicles that facilitate intercellular communication through the transport of proteins, lipids, and nucleic acids. Recent advances in utilizing exosomes as promising vehicles for targeted delivery have opened up numerous opportunities for establishing next-generation exosome-based nanocarriers and therapeutics for multiple biomedical domains. Their inherent biocompatibility, low immunogenicity, nanoscale size and ability to naturally cross biological barriers make them promising alternatives to traditional synthetic drug-delivery systems such as liposomes and polymeric nanoparticles. In this review, we analyzed existing literature and provided an overview of biogenesis, molecular composition, and functional diversity of exosomes followed by a review of recent reports on their application in regenerative therapies and immunomodulation. First, we outlined the role of exosomes in angiogenesis, tissue repair, and immunomodulation. Next, we critically evaluated existing engineering solutions, including isolation techniques, cargo-loading approaches, genetic programming of donor cells, and surface functionalization strategies. Furthermore, we provided a comprehensive overview of recent research on engineered systems that enable controlled release, stability, and multifunctional design of therapeutics, such as exosome-biomaterial hybrids, synthetic exosome mimics, and exosome-nanoparticle platforms. Finally, we highlighted the significant barriers, such as vesicle heterogeneity, optimized production and standardization, and other regulatory challenges in translating exosomal therapeutics from basic research to clinical practice.

Keywords:  Biomaterial engineering; Exosome-based drug delivery; Extracellular vesicles (EVs); Immune modulation; Regenerative medicine

DOI:  https://doi.org/10.1186/s12938-026-01557-y
iScience. 2026 May 15. 29(5): 115641

Oral milk exosome-PLGA nanoparticles enhance anti-tuberculosis efficacy of PBTZ169 and bedaquiline.

Eryue Liu, Chennan Liu, Yangxue Ye, Zimo Wang, Weiyan Zhang, Lei Fu, Bin Wang, Yujin Wang, Yu Lu.

  The oral delivery of next-generation anti-tuberculosis drugs, such as PBTZ169 and bedaquiline (BDQ), is hindered by their poor solubility and low bioavailability. We, here, developed a bioinspired delivery platform that combines milk exosomes with poly(lactic-co-glycolic acid) (PLGA) nanoparticles to deliver the two drugs separately. This nanodelivery system leverages the gastrointestinal stability and mucosal penetration of exosomes, along with the high encapsulation efficiency of PLGA, significantly enhancing drug hydrophilicity and stability. In murine models, the exosome-coated nanoparticles increased plasma bioavailability by 2.5- to 4.9-fold compared with free drugs and achieved superior accumulation in target organs, while mitigating the cardiotoxicity risk associated with BDQ. This synergistic strategy, integrating synthetic and natural carriers, overcomes key pharmacological barriers, offering a promising approach to developing effective and patient-compliant oral therapies for tuberculosis and other potentially infectious diseases.

Keywords:  biological sciences; biotechnology

DOI:  https://doi.org/10.1016/j.isci.2026.115641