Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment

• 作者: Hao Cai Yufan Xiang Yujun Zeng Zhiqian Li Xiuli Zheng Qiang Luo Hongyan Zhu Qiyong Gong Zhongwei Gu Yanhui Liu Hu Zhang Kui Luo
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（2）
• 所属期刊栏目: Original articles
• 页码范围: 544-559
• 页数: 16页
• 语种: 英文

摘要

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 tu-mor 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 signif-icantly reduced gadolinium ion(Gd3+)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 poly-meric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.