한빛사 논문
Abstract
Kyung Hyun Mina, b, 1, Jong-Ho Kimc, 1, Sang Mun Baec, Hyeri Shinc, Min Sang Kimd, Sangjin Parkb, Hyejung Leea, b, Rang-Woon Parkc, In-San Kimc, Kwangmeyung Kimb, Ick Chan Kwonb, Seo Young Jeonga, Doo Sung Leed
a Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
b Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea
c Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, 101 Dongin-Dong, Jung-Gu, Daegu 700-422, Republic of Korea
d Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon, Gyeonggi 440-746, Republic of Korea
1 These authors contributed equally to this paper.
Corresponding authors : Seo Young Jeong, Doo Sung Lee
Abstract
Herein, we evaluated the tumoral low pH targeting characteristics of pH-responsive polymer micelles in cancer targeting therapy. To design the pH-responsive polymeric micelles, hydrophilic methyl ether poly(ethylene glycol) (MPEG) and pH-responsive/biodegradable poly(β-amino ester) (PAE) were copolymerized using a Michael-type step polymerization, resulting in an MEPG-PAE block copolymer. The amphiphilic MPEG-PAE block copolymer formed polymeric micelles with nano-sized diameter by self-assembly, which showed a sharp pH-dependant micellization/demicellization transition at the tumoral acidic pH value (pH 6.4). For the cancer image and therapy, fluorescence dye, tetramethylrhodamine isothiocyanate (TRITC), or anticancer drug, camptothecin (CPT), was efficiently encapsulated into the pH-responsive polymeric micelles (pH-PMs) by a simple solvent casting method. The TRITC or CPT encapsulated pH-PMs (TRITC-pH-PMs or CPT-pH-PMs) showed rapid release of TRITC or CPT in weakly acidic aqueous (pH 6.4) because they still presented a sharp tumoral acid pH-responsive micellization/demicellization transition. The pH-PMs with 10 wt.% of TRITC could deliver substantially more fluorescence dyes to the target tumor tissue in MDA-MB231 human breast tumor-bearing mice, compared to the control polymeric micelles of PEG-poly(l-lactic acid) (PEG-PLLA). Importantly, CPT-pH-PMs exhibited significantly increased therapeutic efficacy with minimum side effects by other tissues in breast tumor-bearing mice, compared to free CPT and CPT encapsulated PEG-PLLA micelles. The tumoral acidic pH-responsive polymeric micelles are highly useful for cancer targeting therapy.
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