Engineered Exosomes as Advanced Drug Delivery Systems for Cancer Therapy
| Author | Parniyan Esmaili | en |
| Author | Rashed Assaran Ghomi | en |
| Author | Ervin Masoumi Nasab | en |
| Author | Hamed Reza | en |
| Author | Cobra Moradian | en |
| Orcid | Cobra Moradian [0000-0002-3948-4642] | en |
| Issued Date | 2026-03-31 | en |
| Abstract | Context: Cancer remains one of the leading causes of mortality worldwide, and current therapeutic modalities, including chemotherapy, radiotherapy, and immunotherapy, are often limited by systemic toxicity, suboptimal tumor targeting, drug resistance, and inadequate bioavailability. In recent years, exosomes have emerged as promising natural nanocarriers owing to their nanoscale size (30 - 150 nm), high biocompatibility, low immunogenicity, ability to cross biological barriers such as the blood-brain barrier (BBB), and intrinsic capacity for intercellular communication. This review examines recent advances in exosome engineering for targeted anticancer drug delivery. Evidence Acquisition: A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar for studies published from January 2015 to April 2026. This review followed PRISMA guidelines. Studies investigating engineered exosomes for targeted cancer therapy were screened, and 32 peer-reviewed articles met the inclusion criteria. The included literature addressed exosome biogenesis; surface-engineering strategies, including PEGylation, RGD, and GE11 modification; drug-loading methods, including electroporation, sonication, incubation, and extrusion; and the delivery of chemotherapeutics, nucleic acids, CRISPR/Cas9 components, and natural products. Outcomes included loading efficiency, tumor targeting, therapeutic efficacy, and biosafety. Results: Several surface-engineering strategies, including the incorporation of targeting ligands, PEGylation, and genetic modification, can improve tumor specificity and circulation stability. Cargo-loading methods vary with respect to loading efficiency, preservation of exosomal integrity, and maintenance of therapeutic bioactivity. Engineered exosomes have been investigated for the delivery of doxorubicin, paclitaxel, siRNA, miRNA, natural compounds such as celastrol and curcumin, and CRISPR/Cas9 components. Particular attention has focused on strategies to overcome multidrug resistance and enable crossing of the BBB. Despite substantial preclinical progress, major challenges remain, including low loading efficiency, batch-to-batch variability, a lack of standardized production and purification protocols, regulatory gaps, and incomplete long-term biosafety data. Emerging solutions, such as microfluidics-based production, immunomodulatory engineering, and artificial intelligence-assisted ligand design, may facilitate clinical translation. Conclusions: Engineered exosomes represent a promising next-generation platform for targeted cancer therapy. Future progress will depend on the development of scalable manufacturing and purification systems, improved cargo-loading strategies, intelligent stimulus-responsive release systems, standardized regulatory frameworks, and interdisciplinary collaboration. | en |
| DOI | https://doi.org/10.69107/jai-172441 | en |
| URI | https://brieflands.com/journals/jai/articles/172441 | en |
| Keyword | Exosome Engineering | en |
| Keyword | Targeted Drug Delivery | en |
| Keyword | Cancer Therapy | en |
| Keyword | CRISPR/Cas9 | en |
| Keyword | Surface Modification | en |
| Keyword | Extracellular Vesicles | en |
| Keyword | Nanomedicine | en |
| Publisher | Brieflands | en |
| Title | Engineered Exosomes as Advanced Drug Delivery Systems for Cancer Therapy | en |
| Type | Review Article | en |