Cationic drug-derived nanoparticles for multifunctional delivery of anticancer siRNA
- Authors
- Chang, Rae Sung; Suh, Min Sung; Kim, Sunil; Shim, Gayong; Lee, Sangbin; Han, Sung Sik; Lee, Kyung Eun; Jeon, Hyesung; Choi, Han-Gon; Choi, Yongseok; Kim, Chan-Wha; Oh, Yu-Kyoung
- Issue Date
- Dec-2011
- Publisher
- ELSEVIER SCI LTD
- Keywords
- siRNA; Mitoxantrone; Multifunctional nanoparticles; Co-delivery; Anticancer chemo-gene therapy
- Citation
- BIOMATERIALS, v.32, no.36, pp.9785 - 9795
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOMATERIALS
- Volume
- 32
- Number
- 36
- Start Page
- 9785
- End Page
- 9795
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/36367
- DOI
- 10.1016/j.biomaterials.2011.09.017
- ISSN
- 0142-9612
- Abstract
- Combined treatment of anticancer drugs and small interfering RNAs (siRNAs) have emerged as a new modality of anticancer therapy. Here, we describe a co-delivery system of anticancer drugs and siRNA in which anticancer drug-derived lipids form cationic nanoparticles for siRNA complexation. The anticancer drug mitoxantrone (MTO) was conjugated to palmitoleic acid, generating two types of palmitoleyl MTO (Pal-MTO) lipids: monopalmitoleyl MTO (mono-Pal-MTO) and dipalmitoleyl MTO (di-Pal-MTO). Among various lipid compositions of MTO, nanoparticles containing mono-Pal-MTO and di-Pal-MTO at a molar ratio of 1:1 (md11-Pal-MTO nanoparticles) showed the most efficient cellular delivery of siRNA, higher than that of Lipofectamine 2000. Delivery of red fluorescence protein-specific siRNA into B16F10-RFP cells using md11-Pal-MTO nanoparticles reduced the expression of RIP at both mRNA and protein levels, demonstrating silencing of the siRNA target gene. Moreover, delivery of Mcl-1-specific anticancer siRNA (siMcl-1) using md11-Pal-MTO enhanced antitumor activity in vitro, reducing tumor cell viability by 81% compared to a reduction of 68% following Lipofectamine 2000-mediated transfection of siMcl-1. Intratumoral administration of siMcl-1 using md11-Pal-MTO nanoparticles significantly inhibited tumor growth, reducing tumor size by 83% compared to untreated controls. Our results suggest the potential of md11-Pal-MTO multifunctional nanoparticles for co-delivery of anticancer siRNAs for effective combination therapy. (C) 2011 Elsevier Ltd. All rights reserved.
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