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 2024-01-20T16:01:11Z 2024-01-20T16:01:11Z 2021-09-04 2011-12 0142-9612 https://pubs.kist.re.kr/handle/201004/129775 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. English ELSEVIER SCI LTD MESOPOROUS SILICA NANOPARTICLES RNA INTERFERENCE DOWN-REGULATION CARCINOMA CELLS INHIBITS GROWTH GENE DELIVERY CANCER-CELLS CHEMOTHERAPY MCL-1 DOXORUBICIN Cationic drug-derived nanoparticles for multifunctional delivery of anticancer siRNA Article 10.1016/j.biomaterials.2011.09.017 1 BIOMATERIALS, v.32, no.36, pp.9785 - 9795 BIOMATERIALS 32 36 9785 9795 scie scopus 000296821800025 2-s2.0-80054060205 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article MESOPOROUS SILICA NANOPARTICLES RNA INTERFERENCE DOWN-REGULATION CARCINOMA CELLS INHIBITS GROWTH GENE DELIVERY CANCER-CELLS CHEMOTHERAPY MCL-1 DOXORUBICIN siRNA Mitoxantrone Multifunctional nanoparticles Co-delivery Anticancer chemo-gene therapy