Affiliation:
1. Henan Province Key Laboratory of New Opto‐electronic Functional Materials Henan Provincial Engineering and Technology Research Center for Precise Synthesis of Fluorine‐Containing Drugs and School of Chemistry and Chemical Engineering Anyang Normal University Anyang Henan 455000 China
2. Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study& Department of Pharmacy and Pharmacology University of South China Hengyang 421001 China
3. College of Chemical Engineering and Technology Tianshui Normal University Tianshui Gansu 741000 China
Abstract
AbstractPoly(tertiary amine‐oxide)‐based polymeric nanocarriers have showed more functionalities than stealthy PEG‐based analogs due to the structure of phospholipid affinitive N‐oxides groups, which has attracted considerable attention to the synthesis of various zwitterionic copolymers with tertiary amine‐oxide grafts for enhanced anticancer drug delivery. However, poly(tertiary amine‐oxide)‐based amphiphilic copolymers with tumor intracellular microenvironment sensitivities, to the knowledge, have been rarely reported likely due to the lack of a controlled synthetic strategy. Herein, a reducible zwitterionic copolymer, poly(ε‐caprolactone)25‐SS‐poly(2‐(N‐oxide‐N,N‐diethylamino)ethyl methacrylate)30 (PCL25‐SS‐OPDEA30) is designed and synthesized successfully via combination of controlled polymerization techniques and post polymerization modification. Specifically, postoxidation of poly(tertiary amine) is confirmed to be a better synthetic strategy toward a well‐defined polymer structure relative to direct polymerization of N,N‐diethylaminoethyl methacrylate (ODEA). The effect of disulfide bridges on the self‐assembly behaviors, in vitro drug loading and drug release properties is investigated in detail. Notablely, the resulting micelles self‐assembled from PCL25‐SS‐OPDEA30 show much greater colloidal stability, higher drug loading content (DLC), and better in vitro tumor cell inhibition than the reduction‐insensitive counterparts. Overall, this study reports a robust strategy toward zwitterionic nanomedicines for on‐demand anticancer drug delivery.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Henan Province
Subject
Materials Chemistry,Organic Chemistry,Polymers and Plastics,Physical and Theoretical Chemistry,Condensed Matter Physics