期刊
MATERIALS CHEMISTRY AND PHYSICS
卷 180, 期 -, 页码 184-194出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.matchemphys.2016.05.062
关键词
Star-branched copolymer; Phosphorylcholine; Polylactic acid; Long circulation; Tumor targeting
资金
- National Nature Science Foundation of China [51303125, 51473119]
Star-branched amphiphilic copolymer nanocarriers with high-density zwitterionic shell show great promise in drug delivery due to their controllable small size and excellent anti-biofouling properties. This gives the hydrophobic cargo with high stability and long blood circulation in vivo. In the present study, star-branched polylactic acid and poly(2-methacryloyloxyethyl phosphorylcholine) copolymers with (AB(3))(3)-type architecture (PIA-b-PMPC3)(3) were conceived as drug vectors, and the copolymers were synthesized by an arm-first approach via the combination of ring opening polymerization (ROP), atom transfer radical polymerization (ATRP) and the click reaction. The self-assembled star-branched copolymer micelles (sCPM) had an average diameter of about 64.5 nm and exhibited an ultra-hydrophilic surface with an ultralow water contact angle of about 12.7 degrees, which efficiently suppressed the adhesion of serum proteins. In vivo experiments showed that the sCPM loading strongly enhanced the blood circulation time of DiI and the plasma half-life of DiI in sCPM was 193 h. The relative accumulation concentration in tumor of DiI delivered by sCPM was 237-fold higher than that of PLA-PEG, at 4 h after intravenous injection. These results demonstrated that the star-branched copolymer (PLA-b-PMPC3)(3) is a promising alternative carrier material for intravenous delivery versus classic PEG-modified strategies. (C) 2016 Elsevier B.V. All rights reserved.
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