Aug 2026· Journal of Controlled Release· Vol 398, pp.
115265
· 0 citations· 226 references
Medicine
TL;DR
This review critically examines exosome sources, isolation and characterization methodologies, cargo-loading strategies, biodistribution, pharmacokinetics, and engineering approaches together with their applications in delivering small-molecule drugs and nucleic acid-based therapeutics to overcome multidrug resistance in cancer.
Abstract
Cancer remains a major global health challenge, with its growing incidence highlighting the critical need for effective and accessible treatments. Current therapeutic approaches, including surgery, chemotherapy, radiation therapy, hormone therapy, and immuno-therapy, are often limited by toxicity, poor targeting, and suboptimal efficacy. These challenges have driven the development of nanotechnology-based strategies aimed at improving tumor selectivity and therapeutic outcomes. Among the most promising are extracellular vesicles, particularly exosomes (30-150 nm), which have garnered significant attention as natural nanocarriers due to their inherent role in intercellular communication and their capacity to encapsulate proteins, nucleic acids, and lipids. Exosomes can be obtained from a wide range of sources, including biological fluids, cell cultures, and unconventional origins such as plants and microorganisms. Of particular interest are milk- and colostrum-derived exosomes, particularly those of bovine origin, have emerged as a promising delivery platform owing to their scalability, biocompatibility, cost-effectiveness and suitability for oral administration. These vesicles possess immunomodulatory properties, demonstrate stability under gastrointestinal conditions, and are readily internalized by intestinal epithelial cells. Furthermore, surface engineering with targeting ligands such as folic acid can enhance tumor specific delivery by exploiting receptor overexpression while minimizing systemic toxicity. This review critically examines exosome sources, isolation and characterization methodologies, cargo-loading strategies, biodistribution, pharmacokinetics, and engineering approaches together with their applications in delivering small-molecule drugs and nucleic acid-based therapeutics to overcome multidrug resistance in cancer. In addition, current challenges related to exosome heterogeneity, manufacturing, quality control, clinical translation, and regulatory considerations are discussed, together with future perspectives for the development of exosome-based therapeutics.
Despite their promise, significant challenges remain, including low cargo-loading efficiency, batch heterogeneity, limited scalability and the absence of standardized manufacturing and regulatory frameworks, future research must address these barriers to accelerate the clinical translation of exosome-based therapeutics.
Elza Karabagh, Babek Alibayov, Adil Allahverdiyev· Expert Reviews in Molecular...· 0 citations
This review highlights the biological characteristics, biogenesis, sources, isolation, purification, and characterization techniques of exosomes, and summarizes the applications of exosome-based drug delivery in cancer, neurological disorders, cardiovascular diseases,inflammatory conditions, infectious diseases, regenerative medicine, and gene therapy.
Snehal Dasharath Pawar, Anis Fathima M S, Nikitha A C et al.· The Bioscan· 0 citations
Extracellular vesicles (EVs) are naturally occurring nanoscale carriers that have gained attention as next-generation platforms for diagnostics, site-specific drug delivery, and tissue engineering owing to their high biocompatibility, minimal immunogenicity, and capacity to transport diverse bioactive cargo across biological barriers. This review discusses the classification, biogenesis, molecular constituents, and therapeutic properties of the major EV subtypes such as exosomes, microvesicles, and apoptotic bodies. It also highlights recent advances in EV engineering for cancer treatment, emphasizing immune modulation and targeted therapeutic delivery. Particular attention is given to plant-derived EVs, which have shown promise as scalable, low-toxicity nanotherapeutics with inherent bioactivity and effective drug delivery potential. Selected preclinical studies, recent patents, and ongoing clinical trials are also summarized, providing an up-to-date perspective on the clinical translation of EV-based technologies. Current challenges in EV isolation, characterization, scalable manufacturing, cargo loading, standardization, and regulatory approval, along with future directions for clinical translation, are summarized. Collectively, this review summarizes the growing applicability of EVs as next-generation platforms for precision medicine, targeted drug delivery, and regenerative therapies while identifying the major obstacles that must be addressed to facilitate their successful clinical translation.
Shery Jacob, Namitha Raichel Varkey, S. Boddu et al.· Pharmaceutics· 0 citations
The findings support the therapeutic potential of exosome-based platforms while also highlighting major challenges, including inconsistencies in isolation protocols, limited cargo- loading capacity, targeting specificity, and in vivo stability.
Shatrudhan Prajapati, Shikha Yadav· Current Neurovascular Resear...· 0 citations
A translational framework for overcoming key barriers in pharmaceutical intervention design for oncology applications is outlined, integrating drug delivery engineering, molecular biopharmaceutics, and computational optimization.
Manoj Dalabehera, Shubham K. Chaudhari, Jatin Kumar et al.· Journal of Pharmacy and Scie...· 0 citations
Colon cancer (CC) is a leading cause of cancer-related mortality worldwide, and its poor prognostic outcome can be attributed to factors such as late diagnosis, tumor heterogeneity, and the failure of conventional chemotherapeutic therapies. Biomimetic nanomaterials that can mimic biological behaviors have recently generated transformative drug carriers with higher biocompatibility, evasion of the immune system, and tumor-seeking capabilities. In this review, recent progresses in biomimetic systems are summarized, such as cell membrane-coated nanoparticles, exosome-based carriers, and ligand-modified nanostructures, with a particular focus on their design paradigm and drug delivery mechanisms and the therapeutic potentiality in CC. Although preclinical investigations reveal potential response, translational barriers to clinical application remain considerable including but not limited to scalability in nanomaterial manufacturing, batch variability in produced materials, and regulatory challenges under FD/EMA regulation. Possible solutions involve cost-effective and scalable macrofluidic and automated bioreactor technologies, comprehensive protocols of exosome isolation and nanoparticle characterization, and systemic harmonization with regulatory frameworks for safety and quality at a stage earlier than the end of the process. Future directions towards combining biomimetic nanocarriers with gene-editing tools, immunotherapies, and phytochemical-based agents for synergistic effects, and the development of novel theranostic systems integrating diagnosis and treatment will be pursued. Overcoming these translational hurdles and interdisciplinary collaborations are critical for biomimetic nanomaterials to fulfil their huge potential to move colon cancer therapy closer to a safer, more effective and clinically practicable reality.
