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 2024-01-20T08:01:02Z 2024-01-20T08:01:02Z 2021-09-04 2015-01-28 0168-3659 https://pubs.kist.re.kr/handle/201004/125847 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. English ELSEVIER SCIENCE BV TUMOR-BEARING MICE MULTIDRUG-RESISTANCE POLYMERIZED SIRNA P-GLYCOPROTEIN ANTICANCER DRUG DOXORUBICIN CELLS CHEMOTHERAPY VERAPAMIL ACID Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance Article 10.1016/j.jconrel.2014.11.019 1 JOURNAL OF CONTROLLED RELEASE, v.198, pp.1 - 9 JOURNAL OF CONTROLLED RELEASE 198 1 9 scie scopus 000347618900001 2-s2.0-84918586982 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article TUMOR-BEARING MICE MULTIDRUG-RESISTANCE POLYMERIZED SIRNA P-GLYCOPROTEIN ANTICANCER DRUG DOXORUBICIN CELLS CHEMOTHERAPY VERAPAMIL ACID Glycol chitosan Multi-drug resistance Nanoparticles Polymerized siRNA siRNA delivery