Exosome-mediated delivery of siRNA molecules in cancer therapy: triumphs and challenges
Open accessAbstract
The discovery of novel and innovative therapeutic strategies for cancer treatment and management remains a major global challenge. Exosomes are endogenous nanoscale extracellular vesicles that have garnered increasing attention as innovative vehicles for advanced drug delivery and targeted therapy. The attractive physicochemical and biological properties of exosomes, including increased permeability, biocompatibility, extended half-life in circulation, reduced toxicity and immunogenicity, and multiple functionalization strategies, have made them preferred drug delivery vehicles in cancer and other diseases. Small interfering RNAs (siRNAs) are remarkably able to target any known gene: an attribute harnessed to knock down cancer-associated genes as a viable strategy in cancer management. Extensive research on exosome-mediated delivery of siRNAs for targeting diverse types of cancer has yielded promising results for anticancer therapy, with some formulations progressing through clinical trials. This review catalogs recent advances in exosome-mediated siRNA delivery in several types of cancer, including the manifold benefits and minimal drawbacks of such innovative delivery systems. Additionally, we have highlighted the potential of plant-derived exosomes as innovative drug delivery systems for cancer treatment, offering numerous advantages such as biocompatibility, scalability, and reduced toxicity compared to traditional methods. These exosomes, with their unique characteristics and potential for effective siRNA delivery, represent a significant advancement in nanomedicine and cancer therapeutics. Further exploration of their manufacturing processes and biological mechanisms could significantly advance natural medicine and enhance the efficacy of exosome-based therapies.
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Exosome-based and exosome-mimicking systems have attracted increasing interest because of intrinsic biocompatibility, tumor-homing potential, and ability to facilitate intracellular transport of functional cargo.
“In particular, exosome-based and exosome-mimicking systems have attracted increasing interest because of their intrinsic biocompatibility, tumor-homing potential, and ability to facilitate intracellular transport of functional cargo [106,107,108].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [106]
The Introduction (§§1.1–1.2) says exosomes have attracted increasing attention for their biocompatibility and ability to transfer functional cargo into cells. Section 1.4 describes tumor accumulation through passive targeting and improved tumor targeting through engineering, rather than an unqualified intrinsic tumor-homing ability. The passages address exosomes, not exosome-mimicking systems. (LLM, conf=0.85)
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Long non-coding RNAs in glioblastoma: from molecular drivers to therapeutic targets
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“In particular, exosome-based and exosome-mimicking systems have attracted increasing interest because of their intrinsic biocompatibility, tumor-homing potential, and ability to facilitate intracellular transport of functional cargo [106–108].”
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Exosome Engineering for Targeted Therapy: Tools and Techniques
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RNA therapeutic targeting of recalcitrant and rare cancers
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- Authors
- Ubanako, P., Mirza, S., Ruff, P., & Penny, C.
- Affiliations
- University of the Witwatersrand (ZA)
- Corresponding author
- Penny, Clement
- Venue
- Frontiers in Molecular Biosciences
- Publisher
- Frontiers Media SA
- Published
- 2024-09-17
- Volume
- 11
- Pages
- 1447953-1447953
- ISSN
- 2296-889X (ISSN-L)
- PMC
- PMC11442288
- OpenAlex
- W4402604331
- Cited by
- 68
- References
- 234
- Citations by year
- 2026: 35 · 2025: 31 · 2024: 2
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Molecular Biosciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- exosomes, siRNA delivery, extracellular vesicles, cancer therapy, plant-derived exosomes, gene silencing, targeted drug delivery, nanomedicine, clinical translation
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