Lin Zhiqiang, Ding Junfeng, Chen Xuesi, He Chaoliang
CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 130022, Changchun, Jilin, P. R. China.
University of Science and Technology of China, 230026, Hefei, Anhui, P. R. China.
Chem Asian J. 2023 Apr 17;18(8):e202300021. doi: 10.1002/asia.202300021. Epub 2023 Mar 13.
pH- and temperature-responsive hydrogels have attracted considerable attention due to their responsiveness to dual physiologically-relevant stimuli. In this study, we developed stimuli-responsive hydrogels based on monomethoxy poly(ethylene glycol) (mPEG)-polypeptide block copolymers containing various tertiary amine pendants (EEP-TAs). The EEP-TAs were synthesized via ring-opening copolymerization of α-amino acid N-carboxyanhydrides, and further modified post-polymerization with click chemistry. The EEP-TAs exhibited an α-helix-to-β-sheet transition when the pH was increased from 4.0 to 7.4. At elevated polymer concentrations, aqueous solutions of the EEP-TAs underwent thermo-induced sol-gel phase transitions, which were dependent on the pH. The hydrogels almost fully degraded within 3 weeks in the subcutaneous layer of mice and exhibited good histocompatibility in vivo. Additionally, doxorubicin (DOX)-loaded hydrogels exhibited pH-responsive drug release profiles in vitro, which were composed of rapid release at acidic pH and more sustained release at neutral pH. Thus, these polypeptide hydrogels hold potential as depots for environment-responsive delivery of therapeutic agents.
pH和温度响应性水凝胶因其对两种生理相关刺激的响应性而备受关注。在本研究中，我们基于含有各种叔胺侧基（EEP-TA）的单甲氧基聚（乙二醇）（mPEG）-多肽嵌段共聚物开发了刺激响应性水凝胶。EEP-TA通过α-氨基酸N-羧基酸酐的开环共聚合成，并在聚合后通过点击化学进一步修饰。当pH从4.0增加到7.4时，EEP-TA表现出从α-螺旋到β-折叠的转变。在较高的聚合物浓度下，EEP-TA的水溶液经历热诱导的溶胶-凝胶相变，这取决于pH。该水凝胶在小鼠皮下层3周内几乎完全降解，并且在体内表现出良好的组织相容性。此外，负载阿霉素（DOX）的水凝胶在体外表现出pH响应性药物释放曲线，其由酸性pH下的快速释放和中性pH下的更持续释放组成。因此，这些多肽水凝胶作为治疗剂的环境响应性递送库具有潜力。
