Zhang Yichuan, Gao Quan, Li Weishuo, He Rongkun, Zhu Liwei, Lian Qianjin, Wang Liang, Li Yang, Bradley Mark, Geng Jin
Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518059, China.
Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
JACS Au. 2022 Feb 23;2(3):579-589. doi: 10.1021/jacsau.1c00373. eCollection 2022 Mar 28.
Numerous prodrugs have been developed and used for cancer treatments to reduce side effects and promote efficacy. In this work, we have developed a new photoactivatable prodrug system based on intracellular photoinduced electron transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization. This unique polymerization process provided a platform for the synthesis of structure-predictable polymers with well-defined structures in living cells. The intracellularly generated poly(,-dimethylacrylamide)s were found to induce cell cycle arrest, apoptosis, and necroptosis, inhibit cell proliferation, and reduce cancer cell motilities. This polymerization-based "prodrug" system efficiently inhibits tumor growth and metastasis both and and will promote the development of targeted and directed cancer chemotherapy.
为了减少副作用并提高疗效，人们已经开发并使用了多种前药用于癌症治疗。在这项工作中，我们基于细胞内光诱导电子转移-可逆加成-断裂链转移（PET-RAFT）聚合反应开发了一种新型的光可激活前药系统。这种独特的聚合过程为在活细胞中合成具有明确结构且结构可预测的聚合物提供了一个平台。研究发现，细胞内生成的聚（N，N-二甲基丙烯酰胺）可诱导细胞周期停滞、凋亡和坏死性凋亡，抑制细胞增殖，并降低癌细胞的运动能力。这种基于聚合反应的“前药”系统在体内和体外均能有效抑制肿瘤生长和转移，并将推动靶向和定向癌症化疗的发展。
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