ph敏感型脂质体的制备.docVIP

Biomaterials 35 (2014) 5414e5424 Contents lists available at ScienceDirect Biomaterials journal hom epage: www ./locate/biom aterials pH-Responsive polymer-liposomes for intracellular drug delivery and tumor extracellular matrix switched-on targeted cancer therapy Yi-Ting Chiang a, Chun-Liang Lo a,b,c,* a Department of Biomedical Engineering, National Yang Ming University, Taipei 112, Taiwan, ROC b Biophotonics Molecular Imaging Research Center (BMIRC), National Yang Ming University, Taipei 112, Taiwan, ROC c Biomedical Engineering Research Center, National Yang Ming University, Taipei 112, Taiwan, ROC a r t i c l e i n f o a b s t r a c t Article history: Received 27 February 2014 Accepted 18 March 2014 Available online 4 April 2014 Keywords: Liposomes Polymers Tumor ECM-induced targeting Intracellular drug delivery Cancer therapy This study presents a tumor-extracellular matrix pH-induced targeting liposome (ECM-targeting lipo- somes), crosslinked from methoxy-poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide-co- histidine)-cholesterol copolymers and biotin2-polyethylene glycol crosslinkers by hydrogen bonds to overcome the defects of liposomes. In this study, ECM-targeting liposomes were completely investigated their pH-responsibility, drug releasing behaviors, anticancer ef?ciencies and the time-dependent organ distribution and toxic effects. Experimental results indicate that ECM-targeting liposomes showed rapid drug releasing pro?les in acidic conditions. Because the ECM-targeting liposomes accumulated prefer- entially in tumor, the ECM-targeting liposomes exhibited exceptional anticancer activity in vivo and lower hepatic and renal toxicity. The ECM-targeting liposomes which are switched on the targeting ability in tumor ECM possess potential for future application in anticancer therapy. ó 2014 Elsevier Ltd. All rights reserved. 1. Introduction Liposome, an important drug carrier, has low toxicity and biocompatibility and is widely used in