Cathepsin B-cleavable doxorubicin prodrugs for targeted cancer therapy

作者：Yan-jun Zhong, Lihua Shao, Yan Li · 发表于：International Journal of Oncology · 年份：2012 · DOI：10.3892/ijo.2012.1754 · 被引用次数：152 · 研究领域：Nanoparticle-Based Drug Delivery、Protease and Inhibitor Mechanisms、Glycosylation and Glycoproteins Research

Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs used for the treatment of hematological malignancies, as well as a broad range of solid tumors. However, the clinical applications of this drug have long been limited due to its severe dose‑dependent toxicities. Therefore, DOX derivatives and analogs have been developed to address this issue. A type of DOX prodrug, cleaved by cathepsin B (Cat B), which is highly upregulated in malignant tumors and premalignant lesions, has been developed to achieve a higher DOX concentration in tumor tissue and a lower concentration in normal tissue, so as to enhance the efficacy and reduce toxicity to normal cells. In this review, we focused on Cat B-cleavable DOX prodrugs and discussed the efficacy of these prodrugs, demonstrated by preclinical and clinical developments.