title: Triggered disassembly of hierarchically assembled onion-like micelles into the pristine core-shell micelles via a small change in pH.
abstract: The size and surface property of nanomaterial-based delivery systems administered intravenously play important roles in their cell uptake and in vivo distribution. Both of them should be capable of self-evolution in order to achieve efficient targeting performance. A facile strategy was proposed to manipulate both the size and surface property of polymeric micelles. It was found that the hierarchical assembly between trimethylated chitosan-g-poly(ε-caprolactone) (TMC-PCL) micelles and carboxyethyl chitosan-g-poly(ethylene glycol) (CEC-PEG) could produce onion-like micelles with enlarged size and PEGylated surface. The onion-like micelles could withstand the ionic strength of plasma and competitive exchange with BSA, and abruptly disassemble into the pristine TMC-PCL micelles via a small change in pH. By varying the degree of carboxyethylation, the disassembly pH could be modulated to the range of the tumoral microclimate pH. In contrast with TMC-PCL micelles, which displayed high cytotoxicity and endocytic ability towards C6 glioma cells, the onion-like micelles were cell-friendly and internalized by the cells at a very low level. Doxorubicin was used as a model chemotherapeutic agent and incorporated within TMC-PCL micelles. Dox release from both TMC-PCL micelles and the onion-like micelles was very slow under normal physiological conditions and displayed excellent pH sensitivity. Cell viability of Dox-loaded micelles was also investigated.
authors: Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
authors: Guoqiang
authors: G
authors: Cai
authors: Haiwen
authors: H
authors: Zhang
authors: Peng
authors: P
authors: Liu
authors: Liqun
authors: L
authors: Wang
authors: Hongliang
authors: H
authors: Jiang
mesh_terms: D000478:Alkylation / Q000187:drug effects; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008823:Micelles; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D019697:Onions / Q000737:chemistry*; D009994:Osmolar Concentration; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats
chemical_list: D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D004317:Doxorubicin; D048271:Chitosan