Cai Hao, Xiang Yufan, Zeng Yujun, Li Zhiqian, Zheng Xiuli, Luo Qiang, Zhu Hongyan, Gong Qiyong, Gu Zhongwei, Liu Yanhui, Zhang Hu, Luo Kui
Huaxi MR Research Center (HMRRC), Department of Neurosurgery, and Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China.
Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu 610041, China.
Acta Pharm Sin B. 2021 Feb;11(2):544-559. doi: 10.1016/j.apsb.2020.07.023. Epub 2020 Aug 14.
Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.
用于癌症同步诊断和治疗的多模态疗法正在兴起。由于其多功能性以及能够响应肿瘤特异性微环境控制药物释放，聚合物载体常被用于负载多种药物。通过将一种小的钆螯合物络合、通过组织蛋白酶B响应性连接子连接化疗药物PTX以及将荧光探针脱镁叶绿酸a（Ppa）与支化糖聚合物共价键合，设计并制备了一种诊疗纳米药物。基于支化前药的纳米系统在组织蛋白酶B过表达的肿瘤微环境中可降解，PTX同时释放以发挥其治疗作用。诊疗纳米药物支化糖聚合物-PTX-DOTA-Gd具有延长的循环时间、增强的肿瘤蓄积以及优异的生物相容性，注射后96小时钆离子（Gd）潴留显著减少。支化糖聚合物-PTX-DOTA-Gd在注射后24小时内增强了成像对比度，具有超过90%的肿瘤抑制率，展现出优异的抗肿瘤疗效且无明显的全身毒性。这种基于支化聚合物前药的纳米药物在癌症的安全有效诊断和治疗方面非常有前景。
