Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance

Ji Young Yhee, Seungyong Song, So Jin Lee, Sung Gurl Park, Ki Suk Kim, Myung Goo Kim, Sejin Son, Heebeom Koo, Ick Chan Kwon, Ji Hoon Jeong, Seo Young Jeong, Sun Hwa Kim, Kwang Meyung Kim

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69 Citations (Scopus)

Abstract

P-glycoprotein (Pgp) mediated multi-drug resistance (MDR) is a major cause of failure in chemotherapy. In this study, small interfering RNA (siRNA) for Pgp down-regulation was delivered to tumors to overcome MDR in cancer. To achieve an efficient siRNA delivery in vivo, self-polymerized 5′-end thiol-modified siRNA (poly-siRNA) was incorporated in tumor targeting glycol chitosan nanoparticles. Pgp-targeted poly-siRNA (psi-Pgp) and thiolated glycol chitosan polymers (tGC) formed stable nanoparticles (psi-Pgp-tGC NPs), and the resulting nanoparticles protected siRNA molecules from enzymatic degradation. The psi-Pgp-tGC NPs could release functional siRNA molecules after cellular delivery, and they were able to facilitate siRNA delivery to Adriamycin-resistant breast cancer cells (MCF-7/ADR). After intravenous administration, the psi-Pgp-tGC NPs accumulated in MCF-7/ADR tumors and down-regulated P-gp expression to sensitize cancer cells. Consequently, chemo-siRNA combination therapy significantly inhibited tumor growth without systemic toxicity. These psi-Pgp-tGC NPs showed great potential as a supplementary therapeutic agent for drug-resistant cancer.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalJournal of Controlled Release
Volume198
DOIs
Publication statusPublished - 2015 Jan 28

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Yhee, J. Y., Song, S., Lee, S. J., Park, S. G., Kim, K. S., Kim, M. G., Son, S., Koo, H., Kwon, I. C., Jeong, J. H., Jeong, S. Y., Kim, S. H., & Kim, K. M. (2015). Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance. Journal of Controlled Release, 198, 1-9. https://doi.org/10.1016/j.jconrel.2014.11.019