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

• Published in: Acta pharmaceutica Sinica. B Vol. 11; no. 2; pp. 544 - 559
• Main Authors: Cai, Hao, Xiang, Yufan, Zeng, Yujun, Li, Zhiqian, Zheng, Xiuli, Luo, Qiang, Zhu, Hongyan, Gong, Qiyong, Gu, Zhongwei, Liu, Yanhui, Zhang, Hu, Luo, Kui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2021; Elsevier
• Subjects: Biodegradability; Branched glycopolymers; Drug delivery; Nanomedicine; Original; Stimuli-responsive; Theranostics; Stimuli-responsive; Drug delivery; Biodegradability; Branched glycopolymers; Nanomedicine; Theranostics
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2020.07.023

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 (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 polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer. •A cathepsin B-responsive theranostic nanomedicine (glycopolymer-PTX-DOTA-Gd) based on a branched glycopolymer was prepared.•Glycopolymer-PTX-DOTA-Gd can be specifically degradated and release drug at tumor enviornment.•Glycopolymer-PTX-DOTA-Gd enhance the contrast of magnetic resonance imaging (MRI) at tumor sites.•The nanomedicine have good biocompatibility, excellent tumor targeting and anti-tumor efficacy. Cathepsin B-responsive biodegradable branched glycopolymer-based prodrug was designed and prepared as theranostic nanomedicine for cancer treatments, resulting in significantly enhanced therapeutic indexes and strengthened contrast of magnetic resonance imaging (MRI) at tumor sites. [Display omitted]