Facile fabrication of core cross-linked micelles by RAFT polymerization and enzyme-mediated reaction.
Polymeric micelles formed in aqueous solution by assembly of amphiphilic block copolymers have been extensively investigated due to their great potential as drug carriers. However, the stability of polymeric assembly is still one of the major challenges in delivering drugs to tissues and cells. Here, we report a facile route to fabricate core cross-linked (CCL) micelles using an enzymatic polymerization as the cross-linking method. We present synthesis of poly(ethylene glycol)-block-poly(N-isopropyl acrylamide-co-N-(4-hydroxyphenethyl) acrylamide) diblock copolymer PEG-b-P(NIPAAm-co-NHPAAm) via reversible addition-fragmentation chain transfer (RAFT) polymerization. The diblock copolymer was then self-assembled into non-cross-linked (NCL) micelles upon heating above the lower critical solution temperature (LCST), and subsequently cross-linked using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) as enzyme and oxidant. The characterization of the diblock copolymer and micelles were studied by NMR, DLS, UV-vis, and fluorescence spectroscopy. The fluorescence study reveals that the cross-linking process endows the micelles with much lower critical micelle concentration (CMC). In addition, the drug release study shows that the CCL micelles have lower release amount of doxorubicin (DOX) than the NCL micelles due to the enhanced stability of the CCL micelles by core cross-linking process.
Key Laboratory of Functional Polymer Materials of Ministry of Education and Institute of Polymer Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China.
Yukun
Y
Wu
Key Laboratory of Functional Polymer Materials of Ministry of Education and Institute of Polymer Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China.
Quanyong
Q
Lai
Key Laboratory of Functional Polymer Materials of Ministry of Education and Institute of Polymer Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China.
Shuqi
S
Lai
Key Laboratory of Functional Polymer Materials of Ministry of Education and Institute of Polymer Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China.
Jing
J
Wu
Key Laboratory of Functional Polymer Materials of Ministry of Education and Institute of Polymer Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China.
Wei
W
Wang
Key Laboratory of Functional Polymer Materials of Ministry of Education and Institute of Polymer Chemistry, Nankai University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China. Electronic address: zhiy@nankai.edu.cn.
Zhi
Z
Yuan
D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry*; D057446:Hydrodynamics; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D058105:Polymerization; D012542:Scattering, Radiation; D013696:Temperature
D000178:Acrylamides; D003432:Cross-Linking Reagents; D008823:Micelles; D011092:Polyethylene Glycols; C067295:N-isopropylacrylamide
Core cross-linked micelles; Enzymatic reaction; Horseradish peroxidase; Self-assembly