Yin Bowen, Wang Ruoxue, Guo Yu, Li Liuxuan, Hu Xiuli
Institute of Polymer Science and Engineering, School of Chemical Engineering, Hebei University of Technology, Tianjin 300130, China.
Polymers (Basel). 2024 Apr 26;16(9):1221. doi: 10.3390/polym16091221.
Endogenous stimuli-responsive injectable hydrogels hold significant promise for practical applications due to their spatio-temporal controllable drug delivery. Herein, we report a facile strategy to construct a series of in situ formation polypeptide hydrogels with thermal responsiveness and enzyme-triggered dynamic self-assembly. The thermo-responsive hydrogels are from the diblock random copolymer mPEG-b-P(Glu-co-Tyr). The L-glutamic acid (Glu) segments with different γ-alkyl groups, including methyl, ethyl, and n-butyl, offer specific secondary structure, facilitating the formation of hydrogel. The L-tyrosine (Tyr) residues not only provide hydrogen-bond interactions and thus adjust the sol-gel transition temperatures, but also endow polypeptide enzyme-responsive properties. The PTyr segments could be phosphorylated, and the phosphotyrosine copolymers were amphiphilies, which could readily self-assemble into spherical aggregates and transform into sheet-like structures upon dephosphorylation by alkaline phosphatase (ALP). P(MGlu-co-Tyr/P) and P(MGlu-co-Tyr) copolymers showed good compatibility with both MC3T3-E1 and Hela cells, with cell viability above 80% at concentrations up to 1000 μg/mL. The prepared injectable polypeptide hydrogel and its enzyme-triggered self-assemblies show particular potential for biomedical applications.
内源性刺激响应性可注射水凝胶因其时空可控的药物递送而在实际应用中具有巨大潜力。在此，我们报告了一种简便的策略，用于构建一系列具有热响应性和酶触发动态自组装的原位形成多肽水凝胶。热响应性水凝胶由二嵌段无规共聚物mPEG-b-P(Glu-co-Tyr)制成。具有不同γ-烷基（包括甲基、乙基和正丁基）的L-谷氨酸（Glu）链段提供特定的二级结构，有助于水凝胶的形成。L-酪氨酸（Tyr）残基不仅提供氢键相互作用，从而调节溶胶-凝胶转变温度，还赋予多肽酶响应特性。PTyr链段可以被磷酸化，磷酸化酪氨酸共聚物是两亲性的，在碱性磷酸酶（ALP）去磷酸化后可以很容易地自组装成球形聚集体并转变为片状结构。P(MGlu-co-Tyr/P)和P(MGlu-co-Tyr)共聚物与MC3T3-E1和Hela细胞均表现出良好的相容性，在浓度高达1000 μg/mL时细胞活力高于80%。所制备的可注射多肽水凝胶及其酶触发的自组装体在生物医学应用中显示出特殊的潜力。
