文献类型：期刊文献

英文题名：Polypeptide-Based "Smart" Micelles for Dual-Drug Delivery: A Combination Study of Experiments and Simulations

作者：Chen, Lili[1];Jiang, Tao[1];Cai, Chunhua[1];Wang, Liquan[1];Lin, Jiaping[1];Cao, Xuguang[1]

机构：[1]E China Univ Sci & Technol, Shanghai Key Lab Adv Polymer Mat, Sch Mat Sci & Engn, Key Lab Ultrafine Mat,Minist Educ, Shanghai 200237, Peoples R China

年份：2014

卷号：3

期号：9

起止页码：1508

外文期刊名：ADVANCED HEALTHCARE MATERIALS

收录：;EI(收录号：20210209759153);WOS:【SCI-EXPANDED(收录号:WOS:000341907800020)】；

基金：This work was supported by National Natural Science Foundation of China (21234002 and 51303055), Key Grant Project of Ministry of Education (313020), National Basic Research Program of China (No. 2012CB933600) and Research Fund for the Doctoral Program of Higher Education of China (20120074120001). Support from projects of Shanghai municipality (10GG15 and 12ZR1442500) and Fundamental Research Funds for the Central Universities (WD1214008) are also appreciated.

语种：英文

外文关键词：drug delivery; micelles; polypeptides; DPD simulation

摘要：A dual-drug-loaded micelle is designed and constructed from a mixture of poly(propylene oxide)-b-poly(-benzyl-l-glutamate)-b-poly(ethylene glycol) (PPO-b-PBLG-b-PEG) triblock terpolymers and two model drugs, doxorubicin (DOX) and naproxen (Nap). In the micelles, the DOX is chemically linked to the PBLG backbones through an acid-cleavable hydrazone bond, whereas the Nap is physically encapsulated in the cores. The drug loading and releasing behaviors of the dual-drug-loaded micelles as well as single drug-loaded micelles (DOX-conjugated or Nap-loaded micelles) are studied. The structures of micelles are characterized by means of microscopies and dynamic light scattering, and further examined by dissipative particle dynamics (DPD) simulations. It is revealed that the micelles possess a core-shell-corona structure in which the PPO/Nap, PBLG/DOX, and PEG aggregate to form the core, shell, and corona, respectively. In vitro studies reveal that the release of DOX and Nap is pH- and thermosensitive. Such drug releasing behaviors are also examined by DPD simulations, and more information regarding the mechanism is obtained. In addition, the bio-related properties such as cellular uptake of the micelles and biocompatibility of the deliveries are evaluated. The results show that the dual-drug-loaded micelles are biocompatible at normal physiological conditions and retain the anti-cancer efficiency.