Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance
- Authors
- Yhee, Ji Young; Song, Seungyong; Lee, So Jin; Park, Sung-Gurl; Kim, Ki-Suk; Kim, Myung Goo; Son, Sejin; Koo, Heebeom; Kwon, Ick Chan; Jeong, Ji Hoon; Jeong, Seo Young; Kim, Sun Hwa; Kim, Kwangmeyung
- Issue Date
- 28-1월-2015
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Glycol chitosan; Multi-drug resistance; Nanoparticles; Polymerized siRNA; siRNA delivery
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.198, pp.1 - 9
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 198
- Start Page
- 1
- End Page
- 9
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/94610
- DOI
- 10.1016/j.jconrel.2014.11.019
- ISSN
- 0168-3659
- 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. (C) 2014 Elsevier B.V. All rights reserved.
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Collections - Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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