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

Hanhee Cho, Man Kyu Shim, Suah Yang, Sukyung Song, Yujeong Moon, Jinseong Kim, Youngro Byun, Cheol Hee Ahn, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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 maintain-ing 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.

Original languageEnglish
Article number83
Issue number1
Publication statusPublished - 2022 Jan

Bibliographical note

Funding Information:
Funding: This work was supported from the National Research Foundation (NRF) of South Korea, funded by the Ministry of Science (NRF-2019R1A2C3006283 and NRF-2021R1C1C2005460) of the Republic of Korea, the KU-KIST Graduate School of Converging Science and Technology (Korea University), and the Intramural Research Program of KIST.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Albumin
  • Chemotherapy
  • Drug delivery
  • Prodrug
  • Targeted therapy

ASJC Scopus subject areas

  • Pharmaceutical Science


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