Cho, Hanhee Shim, Man Kyu Yang, Suah Song, Sukyung Moon, Yujeong Kim, Jinseong Byun, Youngro Ahn, Cheol-Hee Kim, Kwangmeyung 2024-01-19T13:01:19Z 2024-01-19T13:01:19Z 2022-04-05 2022-01 1999-4923 https://pubs.kist.re.kr/handle/201004/115827 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. English MDPI Cathepsin B-Overexpressed Tumor Cell Activatable Albumin-Binding Doxorubicin Prodrug for Cancer-Targeted Therapy Article 10.3390/pharmaceutics14010083 1 PHARMACEUTICS, v.14, no.1 PHARMACEUTICS 14 1 Y scie scopus 000746970700001 2-s2.0-85122136284 Pharmacology & Pharmacy Pharmacology & Pharmacy Article DRUG-DELIVERY prodrug albumin drug delivery targeted therapy chemotherapy