title: Thermo- and pH-responsive copolymers based on PLGA-PEG-PLGA and poly(L-histidine): synthesis and in vitro characterization of copolymer micelles.
abstract: A series of novel thermo- and pH-responsive block copolymers of PHis-PLGA-PEG-PLGA-PHis composed of poly(ethylene glycol) (PEG), poly(D,L-lactide-co-glycolide) (PLGA) and poly(L-histidine) (PHis) were synthesized and used for the construction of stimuli-responsive copolymer micelles. The starting polymers of PLGA-PEG-PLGA and PHis were synthesized by ring-opening polymerization of dl-lactide and glycolide with PEG as an initiator and L-histidine N-carboxylanhydride with isopropylamine as an initiator, respectively. The final copolymer was obtained by the coupling reaction of PHis with PLGA-PEG-PLGA. The copolymer micelles were constructed to have an inner core consisting of two hydrophobic blocks (PLGA and deprotonated PHis) and an outer hydrophilic PEG shell. The temperature- and pH-induced structure changes of the micelles were characterized by an alteration in particle size, a decrease in pyrene fluorescence intensity, and a variation of (1)H NMR spectra in D2O. It was speculated that the hydrophobic-hydrophilic transitions of PEG and PHis in response to temperature and pH variations accounted for the destabilization of micelles. In vitro release profiles, cell cytotoxicity and intracellular location studies further confirmed the temperature- and pH-responsive properties of the copolymer micelles. These results demonstrate the potential of the developed copolymers to be stimuli-responsive carriers for targeted delivery of anti-cancer drugs.
authors.affiliation: School of Pharmacy, PO Box 42, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.affiliation: School of Pharmacy, PO Box 42, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, People's Republic of China; School of Pharmacy, Medical College of Soochow University, Suzhou, Jiangsu Province 215123, People's Republic of China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: School of Pharmacy, PO Box 42, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Jia
authors.affiliation: School of Pharmacy, PO Box 42, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, People's Republic of China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Gu
authors.affiliation: School of Pharmacy, PO Box 42, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, People's Republic of China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Hu
authors.affiliation: School of Pharmacy, PO Box 42, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, PO Box 42, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province 110016, People's Republic of China. Electronic address: qiaomingxi@163.com.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Qiao
mesh_terms: D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D004317:Doxorubicin / Q000494:pharmacology; D005453:Fluorescence; D006639:Histidine / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D011098:Polyglactin 910 / Q000138:chemical synthesis* / Q000737:chemistry; D058105:Polymerization; D066244:Proton Magnetic Resonance Spectroscopy; D012996:Solutions; D013696:Temperature; D017186:Titrimetry
chemical_list: D008823:Micelles; D012996:Solutions; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); C033223:polyhistidine; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D006639:Histidine; D004317:Doxorubicin
keywords: Copolymer micelles; Poly (l-histidine); Thermoresponsive; Tumor targeting; pH-responsive