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

被引:16
|
作者
Cho, Hanhee [1 ,2 ]
Shim, Man Kyu [1 ]
Yang, Suah [1 ,3 ]
Song, Sukyung [1 ,4 ]
Moon, Yujeong [1 ,5 ]
Kim, Jinseong [1 ,3 ]
Byun, Youngro [6 ]
Ahn, Cheol-Hee [2 ]
Kim, Kwangmeyung [1 ,3 ]
机构
[1] Korea Inst Sci & Technol KIST, Biomed Res Inst, Seoul 02792, South Korea
[2] Seoul Natl Univ, Dept Mat Sci & Engn, Seoul 08826, South Korea
[3] Korea Univ, KU KIST Grad Sch Converging Sci & Technol, Seoul 02841, South Korea
[4] Korea Univ, Dept Biosyst & Biotechnol, Seoul 02841, South Korea
[5] Korea Univ, Dept Bioengn, Seoul 02841, South Korea
[6] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 08826, South Korea
基金
新加坡国家研究基金会;
关键词
prodrug; albumin; drug delivery; targeted therapy; chemotherapy; DRUG-DELIVERY;
D O I
10.3390/pharmaceutics14010083
中图分类号
R9 [药学];
学科分类号
1007 ;
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.
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收藏
页数:13
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