Cathepsin B-Overexpressed Tumor Cell Activatable Albumin-Binding Doxorubicin Prodrug for Cancer-Targeted Therapy

Pharmaceutics

Kwangmeyung Kim¹  Yujeong Moon¹  Man Kyu Shim¹  Hanhee Cho¹  Sukyung Song¹  Jinseong Kim¹  Suah Yang¹  Cheol-Hee Ahn²  Youngro Byun³ 

[1] Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea;Department of Materials Science and Engineering, Seoul National University, Seoul 08826, Korea;Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea;

关键词: prodrug;    albumin;    drug delivery;    targeted therapy;    chemotherapy;   

DOI  :  10.3390/pharmaceutics14010083

来源: DOAJ

【 摘 要 】

Prodrugs are bioreversible medications that should undergo an enzymatic or chemical transformation in the tumor microenvironment to release active drugs, which improve cancer selectivity to reduce toxicities of anticancer drugs. However, such approaches have been challenged by poor therapeutic efficacy attributed to a short half-life and low tumor targeting. Herein, we propose cathepsin B-overexpressed tumor cell activatable albumin-binding doxorubicin prodrug, Al-ProD, that consists of a albumin-binding maleimide group, cathepsin B-cleavable peptide (FRRG), and doxorubicin. The Al-ProD binds to in situ albumin, and albumin-bound Al-ProD indicates high tumor accumulation with prolonged half-life, and selctively releases doxorubicin in cathepsin B-overexpressed tumor cells, inducing a potent antitumor efficacy. Concurrently, toxicity of Al-ProD toward normal tissues with innately low cathepsin B expression is significantly reduced by maintaining an inactive state, thereby increasing the safety of chemotherapy. This study offers a promising approach for effective and safe chemotherapy, which may open new avenues for drug design and translational medicine.

【 授权许可】

Unknown