Binary Prodrug of Dichloroacetic Acid and Doxorubicin with Enhanced Anticancer Activity

Amit Sharma, Jieun Chun, Myung Sun Ji, Sooyeon Lee, Chulhun Kang, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


The inevitable challenge in conventional chemotherapy is to deliver the anticancer drugs to the dense population of tumors cells while minimizing the drug-associated side effects on the normal cells. Cancer cells' preference for glycolysis for energy production is well recognized. Intuitively, taking advantage of such cancer-associated metabolism would be a promising strategy for anticancer drug delivery with minimal side effects. In this investigation, we have designed a binary prodrug PDOX as a sequential drug delivery regimens to realize the combination therapy for cancer. As cancer cells exhibit abrupt metabolism with elevated pyruvate dehydrogenase kinase (PDK) activity, dichloroacetic acid (DCA, a well-known PDK inhibitor) was used in combination with anticancer drug doxorubicin (DOX). The designed molecular prodrug was activated selectively by cancer-associated esterase to deliver DCA and DOX, respectively, and induced synergetic effects. Hence, sequential targeted delivery of molecular prodrug PDOX offers a promising approach to overcome the offside drug toxicity, pharmacokinetics, and biodistribution of individuals and provide an alternative option for cancer treatment.

Original languageEnglish
Pages (from-to)2026-2032
Number of pages7
JournalACS Applied Bio Materials
Issue number3
Publication statusPublished - 2021 Mar 15

Bibliographical note

Funding Information:
This work was supported by CRI (Grant 2009-0081566 and 2018R1A3B1052702, JSK) and NRF (Grant 2017R1A2A2A05069805, CK) of Korea. AS thanks Department of Biotechnology (DBT), New Delhi for prestigious Ramalingaswami fellowship 2019 (Grant No. BT/RLF/Re-entry/59/2018).

Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.


  • cancer
  • doxorubicin
  • drug delivery
  • esterase
  • fluorescence
  • theranostic

ASJC Scopus subject areas

  • General Chemistry
  • Biomaterials
  • Biomedical Engineering
  • Biochemistry, medical


Dive into the research topics of 'Binary Prodrug of Dichloroacetic Acid and Doxorubicin with Enhanced Anticancer Activity'. Together they form a unique fingerprint.

Cite this