---
title: "Exosome-mediated siRNA delivery in cancer: loading strategies, targeting approaches, and therapeut"
id: "pubmed-42545436"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42545436"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42545436/"
doi: "10.1007/s40199-026-00631-z"
published_at: "2026-08-03T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Exosome-mediated siRNA delivery in cancer: loading strategies, targeting approaches, and therapeut
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42545436
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42545436/)
- **DOI:** [10.1007/s40199-026-00631-z](https://doi.org/10.1007%2Fs40199-026-00631-z)
- **Published At:** 2026-08-03T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Exosome-mediated delivery of **siRNA** is presented as a promising cancer therapy that enables targeted **gene silencing** with reduced off-target effects. - **Exosomes**, naturally secreted extracellular vesicles, protect siRNA from enzymatic degradation and support cellular uptake by tumor cells. - Natural tropism of exosomes is mediated by surface proteins including **integrins** and **tetraspanins**, which promote tumor microenvironment interactions and cellular adhesion. - Preclinical studies report that exosome-delivered siRNAs can suppress oncogenes, inhibit tumor growth, reverse chemoresistance, and modulate immune and stromal components. - Engineering and loading approaches such as surface functionalization and hybrid exosome–nanoparticle systems enhance stability, payload capacity, and tumor homing. - Combination regimens pairing exosome-siRNA with chemotherapy, immunotherapy, or phototherapy show synergistic effects: blocking survival pathways, promoting apoptosis, and remodeling immunosuppressive niches. - Early-phase clinical studies have indicated acceptable safety, favorable biodistribution, and measurable functional gene silencing, supporting translational potential. - Remaining challenges highlighted include scalable production, cargo heterogeneity, and regulatory considerations; advances in engineering and patient-derived vesicles are proposed as paths to address these barriers. - The review synthesizes current knowledge on loading strategies, targeting maneuvers, therapeutic outcomes, and translational prospects for **exosome-mediated siRNA therapeutics** in cancer.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Internal Medicine, Diabetes, Endocrinology and Metabolism, Mansoura University, Mansoura, Egypt. sehrawyamr@gmail.com. * 2 Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al-Maarif, Anbar, Iraq. * 3 Jizzakh State Pedagogical University, Jizzakh, Uzbekistan. * 4 College of Pharmacy, Dept of Pharmacy Practice, Dubai Medical University, Dubai, United Arab Emirates. * 5 Faculty of Pharmacy, Gokul Global University, Sidhpur, Gujarat, India. * 6 Department of Medical Oncology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, 751003, India. * 7 Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University, Najaf, Iraq. * 8 University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India. * 9 Sharda School of Pharmacy, Sharda University, Greater Noida, India. * 10 Department of Medical Student, Albatterjee College, Jeddah, Saudi Arabia. * PMID: **42545436** * DOI: [ 10.1007/s40199-026-00631-z ](https://doi.org/10.1007/s40199-026-00631-z) Item in Clipboard Review # Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes Amr Ali Mohamed Abdelgawwad El-Sehrawy et al. Daru. 2026. Show details Display options Display options Format Abstract PubMed PMID Daru Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Daru%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Daru%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42545436/) . 2026 Aug 3;34(2):55. doi: 10.1007/s40199-026-00631-z. ### Authors [Amr Ali Mohamed Abdelgawwad El-Sehrawy](https://pubmed.ncbi.nlm.nih.gov/?term=Abdelgawwad+El-Sehrawy+AAM&cauthor_id=42545436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-1 "Internal Medicine, Diabetes, Endocrinology and Metabolism, Mansoura University, Mansoura, Egypt. sehrawyamr@gmail.com."), [Hassan Youssef Hussein](https://pubmed.ncbi.nlm.nih.gov/?term=Youssef+Hussein+H&cauthor_id=42545436)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-2 "Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al-Maarif, Anbar, Iraq."), [Ozodbek Nematov](https://pubmed.ncbi.nlm.nih.gov/?term=Nematov+O&cauthor_id=42545436)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-3 "Jizzakh State Pedagogical University, Jizzakh, Uzbekistan."), [Mirza R Baig](https://pubmed.ncbi.nlm.nih.gov/?term=Baig+MR&cauthor_id=42545436)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-4 "College of Pharmacy, Dept of Pharmacy Practice, Dubai Medical University, Dubai, United Arab Emirates."), [Dhara N Patel](https://pubmed.ncbi.nlm.nih.gov/?term=Patel+DN&cauthor_id=42545436)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-5 "Faculty of Pharmacy, Gokul Global University, Sidhpur, Gujarat, India."), [Priya Priyadarshini Nayak](https://pubmed.ncbi.nlm.nih.gov/?term=Priyadarshini+Nayak+P&cauthor_id=42545436)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-6 "Department of Medical Oncology, IMS and SUM Hospital, Siksha 'O' Anusandhan \(Deemed to be University\), Bhubaneswar, Odisha, 751003, India."), [Safa Alkayyat](https://pubmed.ncbi.nlm.nih.gov/?term=Alkayyat+S&cauthor_id=42545436)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-7 "Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University, Najaf, Iraq."), [Neeraj Bainsal](https://pubmed.ncbi.nlm.nih.gov/?term=Bainsal+N&cauthor_id=42545436)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-8 "University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India."), [Gunjan Singh](https://pubmed.ncbi.nlm.nih.gov/?term=Singh+G&cauthor_id=42545436)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-9 "Sharda School of Pharmacy, Sharda University, Greater Noida, India."), [Tina Saeed Basunduwah](https://pubmed.ncbi.nlm.nih.gov/?term=Basunduwah+TS&cauthor_id=42545436)[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42545436/#short-view-affiliation-10 "Department of Medical Student, Albatterjee College, Jeddah, Saudi Arabia.") ### Affiliations * 1 Internal Medicine, Diabetes, Endocrinology and Metabolism, Mansoura University, Mansoura, Egypt. sehrawyamr@gmail.com. * 2 Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al-Maarif, Anbar, Iraq. * 3 Jizzakh State Pedagogical University, Jizzakh, Uzbekistan. * 4 College of Pharmacy, Dept of Pharmacy Practice, Dubai Medical University, Dubai, United Arab Emirates. * 5 Faculty of Pharmacy, Gokul Global University, Sidhpur, Gujarat, India. * 6 Department of Medical Oncology, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha, 751003, India. * 7 Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University, Najaf, Iraq. * 8 University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India. * 9 Sharda School of Pharmacy, Sharda University, Greater Noida, India. * 10 Department of Medical Student, Albatterjee College, Jeddah, Saudi Arabia. * PMID: **42545436** * DOI: [ 10.1007/s40199-026-00631-z ](https://doi.org/10.1007/s40199-026-00631-z) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Exosome-mediated delivery of small interfering RNA (siRNA) has emerged as a promising therapeutic strategy for cancer treatment, offering precise gene silencing with minimal off-target effects. Exosomes, naturally secreted extracellular vesicles, provide biocompatible carriers that protect siRNA from enzymatic degradation and facilitate efficient uptake by tumor cells. Their natural tropism, driven by surface proteins such as integrins and tetraspanins, promotes cellular adhesion and interactions within the tumor microenvironment, facilitating the delivery of therapeutic cargo. Preclinical studies have demonstrated that exosome-delivered siRNAs can suppress oncogenes, inhibit tumor growth, reverse chemoresistance, and modulate immune responses by targeting stromal and immune components. Engineering approaches, including surface functionalization and hybrid exosome-nanoparticle systems, further enhance stability, payload capacity, and tumor-homing efficiency. Combination strategies with chemotherapy, immunotherapy, or phototherapy have shown synergistic effects, allowing simultaneous inhibition of survival pathways, promotion of apoptosis, and remodeling of the immunosuppressive microenvironment. Early-phase clinical studies indicate safety, effective biodistribution, and functional gene silencing, highlighting the translational potential of exosome-mediated siRNA therapeutics. Challenges such as scalable production, cargo heterogeneity, and regulatory considerations remain, but ongoing advances in exosome engineering and patient-derived vesicles are poised to overcome these barriers. This review aims to comprehensively summarize the current state, therapeutic applications, and translational prospects of exosome-mediated siRNA delivery in cancer. **Keywords:** Cancer treatment; Drug resistance; Exosomes; Gene silencing; Tumor microenvironment; siRNA therapy. © 2026. The Author(s), under exclusive licence to Tehran University of Medical Sciences. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: There is no conflict of interest. Consent to participate: Not applicable. Consent to publish: Not applicable. ## References 1. 1. Bholakant R, Qian H, Zhang J, Huang X, Huang D, Feijen J, Zhong Y, Chen W. Recent Advances of Polycationic siRNA Vectors for Cancer Therapy. Biomacromolecules. 2020;21(8):2966–82. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/32568525/) - [DOI](https://doi.org/10.1021/acs.biomac.0c00438) 2. 1. Bai J, Duan J, Liu R, Du Y, Luo Q, Cui Y, Su Z, Xu J, Xie Y, Lu W. Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells. Asian J Pharm Sci. 2020;15(4):461–71. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/32952669/) 3. 1. Banerjee M, Rajeswari VD. Critical review on the different roles of exosomes in TNBC and exosomal-mediated delivery of microRNA/siRNA/lncRNA and drug targeting signalling pathways in triple-negative breast cancer. Molecules. 2023;28(4):1802. 4. 1. El Moukhtari SH, Garbayo E, Amundarain A, Pascual-Gil S, Carrasco-León A, Prosper F, Agirre X, Blanco-Prieto MJ. Lipid nanoparticles for siRNA delivery in cancer treatment. J Control Release. 2023;361:130–46. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/37532145/) - [DOI](https://doi.org/10.1016/j.jconrel.2023.07.054) 5. 1. Mainini F, Eccles MR. Lipid and polymer-based nanoparticle siRNA delivery systems for cancer therapy. Molecules. 2020;25(11):2692. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/32532030/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/7321291/) - [DOI](https://doi.org/10.3390/molecules25112692) Show all 224 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42545436/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42545436/) * Exosomes* / chemistry Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Exosomes%2Fchemistry%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Exosomes) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42545436/) * Gene Silencing Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Gene+Silencing%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Gene+Silencing) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42545436/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42545436/) * Nanoparticles / chemistry Actions * [ Search in PubMed ](https:
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