Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges
Open accessAbstract
Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.
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Exosomes are inherently non-immunogenic, do not trigger an immune rejection response following implantation, and significantly enhance the safety of treatment.
“In contrast to implanted cells, exosomes are inherently non-immunogenic, signifying that they do not trigger an immune rejection response following implantation, thereby significantly enhancing the safety of the treatment [14].”
From Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation (2025) · cites this paper as [14]
The “Major advantages and disadvantages” section says exosomes may have immunogenic effects depending on their donor cells, contrary to the claim that they are inherently non-immunogenic. Although the small-molecule delivery section describes a low immune response in one setting, the Conclusions say immune reactions and safety still need to be understood; the paper does not establish that exosomes avoid rejection or significantly improve treatment safety. Page numbers are not available in our copy. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredExosomes have been used to deliver small molecules, proteins, and nucleic acids to the brain due to their nonimmunogenic nature.
“Exosomes have been used to deliver small molecules, proteins, and nucleic acids to the brain due to their nonimmunogenic nature; however, there still exist many challenges in the isolation methods, cargo loading procedure, in vivo toxicity, and pharmacokinetics (7, 13).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [13]
The drug-delivery sections report exosome delivery of small-molecule drugs, catalase protein, and siRNA to the brain (pages unavailable). The nucleic-acid section describes exosomes as non-immunogenic to the host, but “Major advantages and disadvantages” cautions that they may cause immune effects depending on their parent cells. Thus, the delivery examples are supported, while the unqualified description of exosomes as nonimmunogenic overstates the source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe engineered exosomes could cross the multiple layers of the blood-brain-barrier and target cancer cells within the brain tissue.
“Importantly, the engineered exosomes could cross the multiple layers of the blood-brain-barrier (BBB) and target cancer cells within the brain tissue (40, 65–68).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [40]
The section on drug delivery vehicles for small molecules (page not available) reports drug distribution in zebrafish brains after exosome delivery across the BBB and improved efficacy in a zebrafish brain-cancer model. It does not establish that the exosomes crossed multiple distinct BBB layers or specifically targeted cancer cells within brain tissue. (LLM, conf=0.85)
Experimental — accuracy not yet measuredExosomes face challenges in isolation methods, cargo loading procedure, in vivo toxicity, and pharmacokinetics.
“Exosomes have been used to deliver small molecules, proteins, and nucleic acids to the brain due to their nonimmunogenic nature; however, there still exist many challenges in the isolation methods, cargo loading procedure, in vivo toxicity, and pharmacokinetics (7, 13).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [13]
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Hassanzadeh, A., Rahman, H. S., Markov, A. A., Endjun, J. J., Zekiy, A. O., Chartrand, M. S., Beheshtkhoo, N., Kouhbanani, M. A. J., Marofi, F., Nikoo, M., et al. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02378-7 · Cited by 190 · see citing works
Extracellular Vesicles and Exosomes: Insights From Exercise Science
Nederveen, J. P., Warnier, G., Carlo, A. D., Nilsson, M. I., & Tarnopolsky, M. A. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.604274 · Cited by 192 · see citing works
- Authors
- Ha, D., Yang, N., & Nadithe, V.
- Affiliations
- Manchester University (US)
- Corresponding author
- Nadithe, Venkatareddy
- ORCID
- Yang, Ningning
- Venue
- Acta Pharmaceutica Sinica B
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 6
- Issue
- 4
- Pages
- 287-296
- ISSN
- 2211-3835 (ISSN-L)
- PMC
- PMC4951582
- OpenAlex
- W2295603197
- Cited by
- 1,346
- References
- 87
- Citations by year
- 2026: 86 · 2025: 137 · 2024: 169 · 2023: 135 · 2022: 160 · 2021: 204 · 2020: 172 · 2019: 137 · 2018: 86 · 2017: 52 · 2016: 7 · 2013: 1
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Pharmaceutica Sinica B (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- 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
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- exosomes, drug carriers, membrane crossing, non-immunogenicity, drug development
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