Acid Sensitive Polymeric Micelles Combining Folate and Bioreducible Conjugate for Specific Intracellular siRNA Delivery

Macromolecular Bioscience
Yanfang YangYuling Liu

Abstract

An efficiently siRNA transporting nanocarrier still remains to be developed. In this study, utilizing the dual stimulus of acid tumor extracellular environment and redox effect of glutathione in the cytosol, a new siRNA transporting system combining triple effects of folate targeting, acid sensitive polymer micelles, and bio-reducible disulfide bond linked siRNA-cell penetrating peptides (CPPs) conjugate is developed to suppress c-myc gene expression of breast cancer (MCF-7 cells) both in vitro and in vivo. Subsequent research demonstrates that the vesicle has particle size of about 100 nm and siRNA entrapment efficiency of approximately 80%. In vitro studies verified over 90% of encapsulated siRNA-CPPs can be released and the vesicle shows higher cellular uptake in response to the tumorous zone. Determination of gene expression at both mRNA and protein levels indicates the constructed vesicle exhibited enhanced cancer cell apoptosis and improved therapeutic efficacy in vitro and in vivo.

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Citations

Mar 21, 2017·Cancer Chemotherapy and Pharmacology·Mahsa Yousefpour Marzbali, Ahmad Yari Khosroushahi
Mar 7, 2020·Pharmaceutics·Rebecca E Taylor, Maliha Zahid
Aug 28, 2021·International Journal of Molecular Sciences·Shabnam TarvirdipourCornelia G Palivan

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