방사선의학 웹진

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Abstract

Combination therapy of nucleic acids and chemical drugs for cancer treatment is a promising strategy to enhance the therapeutic efficacy by simultaneously regulating multiple troublesome pathways. In this study, we report on polyethylene glycol-siRNA-polycaprolactone (PEG-siRNA-PCL) micelles that encapsulate hydrophobic drugs for efficient co-delivery of siRNA and drugs to cancer cells. Amphiphilic PEG-siRNA-PCL copolymers were synthesized by annealing antisense siRNA-PCL conjugates with sense siRNA-PEG conjugates. After paclitaxel encapsulation, PEG-siRNA-PCL micelles containing antiapoptotic Bcl-2-specific siRNA were stabilized with linear polyethylenimine via electrostatic interactions. Stabilized PEG-siRNA-PCL micelles showed superior anticancer effects, assessed by caspase-3 activity analysis, apoptotic cell staining, and a cytotoxicity test, to those of paclitaxel-free PEG-siRNA-PCL micelles and unmodified siRNAs. The strong anticancer activity of paclitaxel-incorporated siRNA micelles can be attributed to the synergistic effect of Bcl-2 siRNA and paclitaxel. This work provides an efficient co-delivery platform for combination anticancer therapy with siRNA and chemotherapy.

Author information

Lee SH1, Lee JY2, Kim JS3, Park TG4, Mok H5.

1Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETHZ) , Vladimir-Prelog-Weg, Zurich 8093, Switzerland.2Basic Research & Innovation Division, AmorePacific Corporation R&D Unit , Yongin 446-729, Republic of Korea.3National Institute of Biomedical Imaging and Bioengineering , 9000 Rockville Pike, Bethesda, Maryland 20892, United States.4Department of Biological Science, Korea Advanced Institute of Science and Technology (KAIST) , Daejeon 305-701, Republic of Korea.5Department of Bioscience and Biotechnology, Konkuk University , Seoul 143-701, Republic of Korea.