Journal
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 15, Issue 3, Pages 531-543Publisher
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2019.2705
Keywords
Gene Delivery; Polypeptide Nanoparticles; Multidrug Resistance; Breast Cancer
Funding
- Key New Drug Creation and Development Program [2018ZX09733001-006]
- National High Technology Research Development Program of China (863) [2014AA020708]
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MDR (multi-drug resistance) is a major obstacle to the successful treatment of cancers. The combination therapeutic based on RNAi has been investigated as a potential strategy for reversing the MDR. However, the effective delivery of siRNA in vivo remains the challenge for the reality of these candidate RNAi drugs. Cationic peptides for gene delivery have attracted considerable attention due to their biocompatibility and high safety. Herein, self-assembled polypeptide nanoparticles LAH4-L1-siRNA (PNLS) were prepared and loaded with a siRNA (siMDR1) for overcoming MDR in human breast cancer MCF-7/ADR cells in vitro and in vivo. Owing to its cationic charges and alpha-helical conformation, the histidine-rich peptide enhanced cellular uptake of siRNA and represented high gene silencing efficiency. The cellular uptake pathways and internalization process of PNLS into cells were further investigated. In vivo biodistribution indicated that the PNLS exhibited higher tumor-targeted delivery. More importantly, PNLS combined with PTX (Paclitaxel) showed antitumor effects and high MDR1 gene silencing efficiency in the tumor-bearing nude mice. Overall, the PNLS achieved the genetargeted knockdown in vivo and hold immense promise for a new therapeutic drug for breast cancer treatment.
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