Citation: Wen-liang Wang, Xiao-jing Ma, Xi-fei Yu. pH-responsive Polymersome Based on PMCP-b-PDPA as a Drug Delivery System to Enhance Cellular Internalization and Intracellular Drug Release[J]. Chinese Journal of Polymer Science, ;2017, 35(11): 1352-1362. doi: 10.1007/s10118-017-1982-x shu

pH-responsive Polymersome Based on PMCP-b-PDPA as a Drug Delivery System to Enhance Cellular Internalization and Intracellular Drug Release

Wen-liang Wang ^a,b ,
Xiao-jing Ma ^a,, ,
Xi-fei Yu ^a,b,,

a.
The Polymer Composites Engineering Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
b.
University of Science and Technology of China, Hefei 230026, China

Corresponding author: Xiao-jing Ma, xjma@ciac.ac.cn Xi-fei Yu, xfyu@ciac.ac.cn
Received Date: 31 March 2017
Revised Date: 13 May 2017
Accepted Date: 17 May 2017

Fund Project: the National Natural Science Foundation of China 21603214the National Natural Science Foundation of China 21674109the National Natural Science Foundation of China 21304096the National Natural Science Foundation of China 21474103

Choline phosphate (CP) as a novel zwitterion possesses specific and excellent properties compared with phosphorylcholine (PC), as well as its polymer, such as poly(2-(methacryloyloxy)ethyl choline phosphate) (PMCP), has been studied extensively due to its unique characteristics of rapid cellular internalization via the special quadrupole interactions with the cell membrane. Recently, we reported a novel PMCP-based drug delivery system to enhance the cellular internalization where the drug was conjugated to the polymer via reversible acylhydrazone bond. Herein, to make full use of this feature of PMCP, we synthesized the diblock copolymer poly(2-(methacryloyloxy)ethyl choline phosphate)-b-poly(2-(diisopropylamino)ethyl methacrylate) (PMCP-b-PDPA), which could self-assemble into polymersomes with hydrophilic PMCP corona and hydrophobic membrane wall in mild conditions when the pH value is ≥ 6.4. It has been found that these polymersomes can be successfully used to load anticancer drug Dox with the loading content of about 11.30 wt%. After the polymersome is rapidly internalized by the cell with the aid of PMCP, the loaded drug can be burst-released in endosomes since PDPA segment is protonated at low pH environment, which renders PDPA to transfer from hydrophobic to hydrophilic, and the subsequent polymersomes collapse thoroughly. Ultimately, the "proton sponge" effect of PDPA chain can further accelerate the Dox to escape from endosome to cytoplasm to exert cytostatic effects. Meanwhile, the cell viability assays showed that the Dox-loaded polymersomes exhibited significant inhibitory effect on tumor cells, indicating its great potential as a targeted intracellular delivery system with high efficiency.
- Drug delivery,
- Choline phosphate,
- Polymersome,
- PDPA,
- Enhanced cellular internalization
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