College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610065, China.
Adv Mater. 2023 Jun;35(24):e2210986. doi: 10.1002/adma.202210986. Epub 2023 Mar 30.
Allosteric transitions can modulate the self-assembly and biological function of proteins. It remains, however, tremendously challenging to design synthetic allosteric polymeric assemblies with spatiotemporally switchable hierarchical structures and functionalities. Here, a photoallosteric polymersome is constructed that undergoes a rapid conformational transition from β-sheet to α-helix upon exposure to near-infrared light irradiation. In addition to improving nanoparticle cell penetration and lysosome escape, photoinduced allosteric behavior reconstructs the vesicular membrane structure, which stimulates the release of hydrophilic cytolytic peptide melittin and hydrophobic kinase inhibitor sorafenib. Combining on-demand delivery of multiple therapeutics with phototherapy results in apoptosis and immunogenic death of tumor cells, remold the immune microenvironment and achieve an excellent synergistic anticancer efficacy in vivo without tumor recurrence and metastasis. Such a light-modulated allosteric transition in non-photosensitive polymers provides new insight into the development of smart nanomaterials for biosensing and drug delivery applications.
别构转变可以调节蛋白质的自组装和生物功能。然而，设计具有时空可控的分级结构和功能的合成别构聚合物组装体仍然极具挑战性。在这里，构建了一种光别构聚合物囊泡，它在近红外光照射下迅速从β-折叠转变为α-螺旋。除了提高纳米颗粒的细胞穿透和溶酶体逃逸能力外，光诱导的别构行为还重建了囊泡膜结构，刺激亲水细胞毒性肽蜂毒素和疏水性激酶抑制剂索拉非尼的释放。将按需递送达多种治疗药物与光疗相结合，导致肿瘤细胞发生凋亡和免疫原性死亡，重塑免疫微环境，在体内实现优异的协同抗癌疗效，而无肿瘤复发和转移。这种非光敏感聚合物中的光调控别构转变为生物传感和药物输送应用的智能纳米材料的发展提供了新的见解。
