title: pH-responsive mechanism of a deoxycholic acid and folate comodified chitosan micelle under cancerous environment.
abstract: Smart pH-responsive polymeric micelles have attracted much attention as one of the most promising drug delivery candidates. In this paper, a different substitution of deoxycholic acid (DCA) and folic acid (FA) comodified hydroxypropyl chitosans (HPCHS) were synthesized for doxorubicin (DOX) targeted delivery and controllable release. The results indicate that the DOX-release behavior is pH-responsive and closely related with the grafting proportions of the two hydrophobic ingredients. The pH-responsive mechanism for the optimized (6%DCA)-HPCHS-(0.1%FA) was suggested, resulting from a synergistic effect of gradual hydrolysis of the amido bond and electrostatic repulsion between the subsequently protonated DOX and the amino residue of the chitosan backbone under a cancerous microenvironment. Moreover, the DOX/(6%DCA)-HPCHS-(0.1%FA) micelle as a promising targeted drug delivery system in cancer therapy was evaluated by cell growth inhibition assays and confocal laser microscopy in vitro. The results clearly demonstrate a controlled release of its cargo and promoted curative efficacy of DOX.
authors: Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors: Daiqin
authors: D
authors: Chen
authors: Peng
authors: P
authors: Song
authors: Feng
authors: F
authors: Jiang
authors: Xiangyue
authors: X
authors: Meng
authors: Weiping
authors: W
authors: Sui
authors: Chunying
authors: C
authors: Shu
authors: Li-Jun
authors: LJ
authors: Wan
mesh_terms: D002214:Capsules; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D003692:Delayed-Action Preparations; D003840:Deoxycholic Acid / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005492:Folic Acid / Q000737:chemistry*; D058972:Folic Acid Transporters / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D058972:Folic Acid Transporters; D008823:Micelles; D003840:Deoxycholic Acid; D004317:Doxorubicin; D048271:Chitosan; D005492:Folic Acid