한빛사 논문
Abstract
Xiang Lan Wu †‡, Jong Ho Kim †∥, Heebeom Koo §, Sang Mun Bae∥ , Hyeri Shin∥ , Min Sang Kim ‡, Byung-Heon Lee∥ , Rang-Woon Park∥ , In-San Kim∥ , Kuiwon Choi §, Ick Chan Kwon §, Kwangmeyung Kim *§ and Doo Sung Lee *‡
Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea, Biomedical Research Center, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul, 136-791, South Korea, and Advanced Medical Technology Cluster for Diagnosis & Prediction, Kyungpook National University, Daegu 700-422, South Korea
* To whom correspondence should be addressed.
† Both authors contributed equally., ‡ Sungkyunkwan University., § Korea Institute of Science and Technology., ∥Kyungpook National University.
Abstract
Herein, we prepared tumor-targeting peptide (AP peptide; CRKRLDRN) conjugated pH-responsive polymeric micelles (pH-PMs) in cancer therapy by active and pH-responsive tumor targeting delivery systems, simultaneously. The active tumor targeting and tumoral pH-responsive polymeric micelles were prepared by mixing AP peptide conjugated PEG-poly(d,l-lactic acid) block copolymer (AP-PEG-PLA) into the pH-responsive micelles of methyl ether poly(ethylene glycol) (MPEG)-poly(β-amino ester) (PAE) block copolymer (MPEG-PAE). These mixed amphiphilic block copolymers were self-assembled to form stable AP peptide-conjugated and pH-responsive AP-PEG-PLA/MPEG-PAE micelles (AP-pH-PMs) with an average size of 150 nm. The AP-pH-PMs containing 10 wt % of AP-PEG-PLA showed a sharp pH-dependent micellization/demicellization transition at the tumoral acid pH. Also, they presented the pH-dependent drug release profile at the acidic pH of 6.4. The fluorescence dye, TRITC, encapsulated AP-pH-PMs (TRITC-AP-pH-PMs) presented the higher tumor-specific targeting ability in vitro cancer cell culture system and in vivo tumor-bearing mice, compared to control pH-responsive micelles of MPEG-PAE. For the cancer therapy, the anticancer drug, doxorubicin (DOX), was efficiently encapsulated into the AP-pH-PMs (DOX-AP-pH-PMs) with a higher loading efficiency. DOX-AP-pH-PMs efficiently deliver anticancer drugs in MDA-MB231 human breast tumor-bearing mice, resulted in excellent anticancer therapeutic efficacy, compared to free DOX and DOX encapsulated MEG-PAE micelles, indicating the excellent tumor targeting ability of AP-pH-PMs. Therefore, these tumor-targeting peptide-conjugated and pH-responsive polymeric micelles have great potential application in cancer therapy.
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