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Nucleolin-targeted Extracellular Vesicles as a Versatile Platform for Biologics Delivery to Breast Cancer
Yayu Wang1, Xiaojia Chen1, Baoqing Tian1
1Institute of Biomedicine & Department of Cell Biology, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine, Guangzhou, China.
Abstract:
Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells. This delivery vesicle targeted let-7 miRNA delivery to MDA-MB-231 cells in vitro as confirmed with fluorescent microscopic imaging and flow cytometry. Also, intravenously delivered AS1411-EVs loaded with miRNA let-7 labeled with the fluorescent marker, Cy5, selectively targeted tumor tissues in tumor-bearing mice and inhibited tumor growth. Importantly, the modified EVs were well tolerated and showed no evidence of nonspecific side effects or immune response. Thus, the RNAi nanoplatform is versatile and can deliver siRNA or miRNA to breast cancer cells both in vitro and in vivo. Our results suggest that the AS1411-EVs have a great potential as drug delivery vehicles to treat cancers.
Insights
Extracellular vesicles modified with AS1411 aptamer effectively deliver small interfering RNAs (siRNA) and microRNAs (miRNA) to breast cancer cells. This novel RNAi nanoplatform shows promise for targeted cancer therapy with minimal side effects.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Small interfering RNAs (siRNA) and microRNAs (miRNA) show therapeutic promise but require effective delivery systems.
- Extracellular vesicles (EVs) are natural carriers for intercellular communication, suitable for delivering nucleic acids.
Purpose of the Study:
- To develop and evaluate AS1411-modified EVs as a targeted delivery system for siRNA/miRNA in breast cancer.
- To assess the efficacy and safety of this RNAi nanoplatform in vitro and in vivo.
Main Methods:
- Engineered extracellular vesicles (EVs) with the AS1411 aptamer for targeting nucleolin on breast cancer cells.
- Delivered let-7 miRNA encapsulated in AS1411-EVs to MDA-MB-231 cells in vitro and to tumor-bearing mice in vivo.
- Assessed delivery efficiency using fluorescent microscopy and flow cytometry; evaluated tumor growth inhibition and safety.
Main Results:
- AS1411-modified EVs successfully delivered let-7 miRNA to MDA-MB-231 cells in vitro.
- Intravenously administered AS1411-EVs selectively targeted tumor tissues in mice and inhibited tumor growth.
- The modified EVs demonstrated good tolerability with no significant side effects or immune responses observed.
Conclusions:
- AS1411-modified EVs serve as a versatile and effective nanoplatform for targeted delivery of siRNA and miRNA to breast cancer.
- This approach holds significant potential for developing novel cancer therapeutics with improved targeting and safety profiles.
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