title: Folic acid-conjugated pH/temperature/redox multi-stimuli responsive polymer microspheres for delivery of anti-cancer drug.
abstract: The folic acid (FA)-conjugated pH/temperature/redox multi-stimuli responsive poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine/poly(N-isopropylacrylamide-co-glycidyl methacrylate-co-N,N-bis(acryloyl)cystamine) microspheres were prepared by a two-stage distillation-precipitation polymerization with subsequent surface modification with FA. The microspheres were characterized by transmission electron microscopy, dynamical light scattering, Fourier-transform infrared spectra, UV-vis spectra and elemental analysis. The degradation of the functional microspheres could be triggered by a reductive reagent, such as glutathione, due to presence of BAC crosslinker. The drug-loaded microspheres exhibited a pH/temperature/redox multi-stimuli responsive drug release character for doxorubicin hydrochloride as a model anti-cancer drug, which was efficiently loaded into the microspheres with a high loading capacity of 208.0% and an encapsulation efficiency of 85.4%. In vitro drug delivery study indicated that the FA-conjugated microspheres could deliver Dox into MCF-7 cells more efficiently than the microspheres without functionalization of FA. Furthermore, WST-1 assay showed that the microspheres had no obvious toxicity to MCF-7 cells even at a high concentration of 2000 μg mL(-1). The resultant microsphere may be a promising vector for delivery of anti-cancer drugs as it exhibits a low cytotoxicity and degradability, precise molecular targeting property and multi-stimuli responsively controlled drug release.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Basic Medical Research Center, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Basic Medical Research Center, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Fuli
authors.initials: F
authors.lastname: Feng
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Basic Medical Research Center, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Yinsong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Basic Medical Research Center, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China. Electronic address: yangxiaoying@tijmu.edu.cn.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, PR China. Electronic address: xlyang88@nankai.edu.cn.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Basic Medical Research Center, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004337:Drug Carriers; D005492:Folic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D046529:Microscopy, Electron, Transmission; D008863:Microspheres; D010084:Oxidation-Reduction; D011108:Polymers / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D005492:Folic Acid
keywords: Distillation–precipitation polymerization; Drug delivery; Folic acid-conjugated; pH/temperature/redox multi-stimuli responsive