title: Synthesis and evaluation of cholesterol-grafted PEGylated peptides with pH-triggered property as novel drug carriers for cancer chemotherapy.
abstract: Multifunctional core/shell micelles were self-assembled from triblock copolymers poly(ethylene glycol) methyl ether-b-peptide-g-cholesterol (mPEG-b-P-g-Chol) and used as the doxorubicin delivery carriers for cancer chemotherapy. The copolymers were designed and synthesized successfully based on peptides containing histidine residues (pH-trigger) with different topological structures. The peptides were modified by mPEG (hydrophilic) and cholesterol motifs (hydrophobic) on the terminus, resulting in pH-sensitive amphiphilic copolymers. The critical micelle concentrations (CMCs) of the micelles were determined as 4.79, 2.50 and 1.86mg/L for the linear, Y-shape and fork-shape copolymers, respectively, demonstrating the formation of micelle even at low concentration. The pKb values of three copolymers were found to be around 6.1-6.3 by potentiometric titration test, showing the satisfied pH-sensitivity. The average diameter and zeta potential of blank micelles were 170nm and +20mV at pH 7.4, and increased to 250nm and +35mV at pH 5.0. DOX was loaded into the core of polymeric micelles by dialysis method, and the drug loading capacity slightly increased when the copolymer topological structure changed from linear to Y- and fork-shape. The drug release rate from the system was obviously influencing by the pH values according to the results of in vitro DOX release experiment. Moreover, to investigate the structure-property relationship, the drug release mechanism was preliminarily explored by the semi-empirical equations. Toxicity test showed that three copolymers had bare toxicity whereas the DOX-loaded micelles remained high cytotoxicity for tumor cells. The results indicate the synthesized copolymers might be a potential hydrophobic drug delivery carrier for cancer targeting therapy with controlled drug release.
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, 510640 Guangzhou, People's Republic of China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
authors.forename: Can Yang
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, 510640 Guangzhou, People's Republic of China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, 510640 Guangzhou, People's Republic of China.
authors.forename: Wen Sheng
authors.initials: WS
authors.lastname: Wu
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, 510640 Guangzhou, People's Republic of China.
authors.forename: Xin Dong
authors.initials: XD
authors.lastname: Guo
authors.affiliation: Department of Chemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Cheng Zhi
authors.initials: CZ
authors.lastname: Cai
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, 510640 Guangzhou, People's Republic of China. Electronic address: celjzh@scut.edu.cn.
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000378:metabolism; D013499:Surface Properties
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; C118255:polyethylene glycol-cholesterol; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol
keywords: Amphiphilic; Cancer chemotherapy; Drug delivery; Micelle; Peptides; pH-triggered