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.
Abstract
Content of image described in text. Abstract Background Gene therapy has emerged as a transformative approach for treating diseases that are caused by genetic defects, including cancer, inherited metabolic disorders and immunodeficiencies. However, its clinical success depends critically on the availability of safe, efficient and non-immunogenic delivery systems. Conventional viral vectors, while highly effective, are associated with immunogenicity, oncogenic risk and high production costs. Non-viral alternatives offer improved safety but they have lower transfection efficiency and limited stability. Exosomes are naturally secreted, endosome-derived nanovesicles ranging from 30–150 nm in diameter and have emerged as promising next-generation carriers for gene and drug delivery. Their inherent biocompatibility, low immunogenicity, ability to cross biological barriers and capacity to transport diverse molecular cargo including nucleic acids, proteins and small molecules make them particularly attractive as therapeutic platforms. Methods This review summarizes the biogenesis, molecular composition and classification of exosomes and examines their applications in siRNA/miRNA delivery, CRISPR/Cas9 gene editing, mRNA therapy, cancer treatment and vaccine development. Special attention is given to engineered, plant-derived and stem cell-derived exosomes, as well as current cargo-loading strategies and commercial therapeutic platforms. Results Despite their promise, significant challenges remain, including low cargo-loading efficiency, batch heterogeneity, limited scalability and the absence of standardized manufacturing and regulatory frameworks. Conclusions Future research must address these barriers to accelerate the clinical translation of exosome-based therapeutics.
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.
Yaseera Arif, D. N. Moholkar, Raghuram Kandimalla et al.· Journal of Controlled Releas...· 0 citations
Exosome-based drug delivery systems have emerged as a promising platform for targeted therapeuticsand precision medicine because of their excellent biocompatibility, low immunogenicity, and intrinsicability to transport diverse therapeutic molecules. Unlike conventional nanocarriers, exosomesefficiently deliver proteins, nucleic acids, and small-molecule drugs while overcoming biologicalbarriers, including the blood–brain barrier. This review highlights the biological characteristics,biogenesis, sources, isolation, purification, and characterization techniques of exosomes. It alsodiscusses recent advances in drug-loading strategies, surface engineering, and exosome modification toimprove targeting efficiency and therapeutic performance. Furthermore, the review summarizes theapplications of exosome-based drug delivery in cancer, neurological disorders, cardiovascular diseases,inflammatory conditions, infectious diseases, regenerative medicine, and gene therapy. Despite theirremarkable therapeutic potential, challenges related to large-scale production, standardization, storagestability, and regulatory approval remain significant barriers to clinical translation. Continued researchand technological advancements are expected to facilitate the successful integration of exosome-basedtherapeutics into personalized healthcare.
Snehal Dasharath Pawar, Anis Fathima M S, Nikitha A C et al.· The Bioscan· 0 citations
Cervical cancer pharmacotherapy is significantly limited by physiological and cellular barriers that restrict drug access to therapeutic targets, resulting in suboptimal biodistribution, systemic toxicity, and the emergence of drug resistance. This review provides a mechanistic and biopharmaceutics-centered analysis of how advanced drug delivery systems are being engineered to overcome these limitations. We critically examine the role of nanocarriers, including lipid-based vesicles, polymeric nanoparticles, and inorganic hybrid systems, in modulating absorption, distribution, and tumor-targeting efficiency, with emphasis on their physicochemical properties and interaction with biological barriers such as the tumor microenvironment and cellular uptake pathways. In parallel, we analyze nucleic acid-based therapeutics (CRISPR/Cas systems, miRNA, and antisense oligonucleotides) from a pharmaceutical sciences perspective, focusing on delivery constraints, stability, intracellular trafficking, and their ability to modulate pharmacological response and drug resistance mechanisms. The review also discusses the integration of immunomodulatory strategies within nanodelivery platforms as a means to alter disease-related biological barriers and improve therapeutic index. Finally, we explore the emerging role of AI-assisted models in optimizing formulation design, predicting pharmacokinetic behavior, and supporting precision dosing strategies in drug development workflows. By integrating drug delivery engineering, molecular biopharmaceutics, and computational optimization, this work outlines a translational framework for overcoming key barriers in pharmaceutical intervention design for oncology applications.
Manoj Dalabehera, Shubham K. Chaudhari, Jatin Kumar et al.· Journal of Pharmacy and Scie...· 0 citations
BACKGROUND
Glioma is one of the most aggressive and treatment-resistant malignancies of the central nervous system, characterized by rapid progression and poor prognosis. Conventional treatment approaches, including surgery, radiotherapy, and chemotherapy, often fail to achieve long-term remission due to the restrictive nature of the blood-brain barrier and the inherent heterogeneity of tumor cells.
METHODS
This review summarizes and critically analyzes current preclinical and clinical evidence on exosome biology, including their biogenesis, molecular cargo, and therapeutic engineering strategies. It further highlights recent advances in exosome-based delivery of chemotherapeutic agents, microRNAs, and gene-editing systems for glioma management.
RESULTS
Tumor- and stem cell-derived exosomes have demonstrated the ability to cross biological barriers while carrying functional biomolecules and modulating the tumor microenvironment. Their inherent stability, low immunogenicity, and capacity for surface modification make them promising nanocarriers for therapeutic applications. Engineered exosomes loaded with anti- tumor microRNAs, small interfering RNAs, or chemotherapeutic nanoparticles have shown promising results in enhancing drug sensitivity and reducing tumor proliferation in experimental glioma models.
DISCUSSION
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. Although exosomes have demonstrated the ability to overcome biological barriers and therapeutic resistance, standardized manufacturing protocols and robust clinical validation remain essential for successful clinical translation.
CONCLUSION
Exosome-based systems represent a promising approach for the diagnosis and treatment of glioma. Their dual role as biomarkers and therapeutic drug carriers offers significant potential for personalized medicine through non-invasive disease monitoring and targeted therapeutic strategies. However, further optimization of large-scale production, purification methods, and clinical translation is necessary before exosome-based therapeutics can be integrated into standard glioma treatment protocols.
Shatrudhan Prajapati, Shikha Yadav· Current Neurovascular Resear...· 0 citations
Malignant tumors, featuring strong heterogeneity, innate immune escape and acquired drug resistance, is the top cause of disease-related death worldwide. Traditional treatments for these cancers have serious drawbacks in terms of therapeutic efficacy and safety. Lipid nanoparticle (LNP) is the most powerful nonviral nucleic acid delivery vector to date and can achieve efficient encapsulation, protection and intracellular delivery of nucleic acid molecules with a biomimetic nanostructure interlinked synergistically assembled by core components, has become a key research vehicle in the field of cancer gene therapy. In this review, we summarize the composition of core functions of the component of LNPs, molecular evolution trajectory, targeting optimization and so on, and system summarize the latest research progress of LNP in targeted delivery of traditional chemotherapeutic agents, specific gene regulation by nucleic acid therapy and combination cancer therapy etc. Collectively, these pieces of work provide a complete academic reference for future fundamental studies and clinical translation of LNP-mediated cancer gene therapy technologies, and lay the theoretical basis for further non-viral nucleic acid vectors used in cancer gene therapy in the wider biomedical field.
Haoze Zhu· International Journal of Bio...· 0 citations
Gene therapy has emerged as one of the most promising approaches in both medical and biotechnological fields due to its capacity to modify, optimize, and regulate target DNA sequences. Recent advancements integrating gene therapy with nanotechnology, particularly through nano-carrier systems, have enabled precise delivery of therapeutic nucleic acids with controlled release at specific pathological sites [1]. Initially focused on monogenic disorders, gene therapy applications have now expanded to a broad spectrum of inherited and acquired diseases [2]. Protein-based nanocarriers have attracted considerable attention as next-generation non-viral vectors due to their intrinsic biocompatibility, biodegradability, and structural versatility [3]. Their ability to encapsulate nucleic acids, support controlled release, and enable targeted delivery makes them attractive candidates for cancer gene therapy. These unique characteristics position protein-based nanocarriers as a cell-friendly and effective strategy for improving the safety and efficiency of gene delivery systems [4]. Consequently, they represent a promising strategy for improving the safety and efficacy of cancer gene therapy. The development of safe, efficient, and biocompatible vectors remains a critical determinant of therapeutic success. Recombinant peptides, despite their therapeutic potential, face challenges such as high toxicity, instability, poor bioavailability, and costly production, which gene therapy strategies aim to overcome [5]. Techniques including gene knockdown, mutation correction, and gene insertion are central to modern gene therapy approaches. This article reviews the recent progress and challenges associated with nano-based non-viral vectors designed for targeted delivery of DNA into cancerous cells.
M. Yousefian, Maryam Baharmast· Journal of Biomaterials Scie...· 0 citations