Synthesis of a phenylboronic ester-linked PEG-lipid conjugate for ROS-responsive drug delivery

• Published in: Polymer chemistry 2017-10, Vol.8 (40), p.6209-6216
• Main Authors: Zhang, Tianhui, Chen, Xin, Xiao, Chunsheng, Zhuang, Xiuli, Chen, Xuesi
• Format: Article
• Language: English
• ISSN: 1759-9954; 1759-9962
• DOI: 10.1039/C7PY00915A

Stimuli-responsive drug delivery systems (DDSs) offering spatial-temporal and dosage controlled transport of drugs in vivo have attracted much attention for anticancer drug delivery. In the present work, a kind of phenylboronic ester-linked PEG-lipid conjugate was designed and synthesized for H 2 O 2 -responsive drug delivery. Firstly, a chain-end alkynyl functionalized methoxy poly(ethylene glycol) with a phenylboronic pinacol ester linker was synthesized via a classical Passerini reaction of carboxyl functionalized methoxy poly(ethylene glycol) 2000 (mPEG 2k -COOH), 4-formylphenylboronic pinacol ester and propargyl isocyanoacetamide. The obtained polymer was denoted as mPEG 2k -PBPE-alkynyl. Then, the oxidation-responsive cleavage of the phenylboronic pinacol ester linker between the mPEG 2k -COOH and alkynyl chain-end was verified by in situ 1 H NMR and mass spectra characterization. Furthermore, the amphiphilic PEG-lipid conjugate was synthesized by the Cu( i )-catalyzed click reaction of mPEG 2k -PBPE-alkynyl and 3-azido-1,2-propanediol distearate (N 3 -DSA). The resultant mPEG 2k -PBPE-DSA could self-assemble into stable micelles in aqueous media. Nile red was used as the model drug and was loaded into the micelles. The obtained drug loaded micelles exhibited a typical H 2 O 2 -responsive drug release behavior and could be effectively internalized by MCF-7 cells. In addition, the synthesized mPEG 2k -PBPE-DSA was tested to be nontoxic towards RAW264.7 cells. Therefore, this biocompatible mPEG 2k -PBPE-DSA conjugate would be promising for applications in ROS-responsive drug delivery.