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

2 Citations (Scopus)

Abstract

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
Volume4
Issue number3
DOIs
Publication statusPublished - 2021 Mar 15

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)
  • Biomaterials
  • Biomedical Engineering
  • Biochemistry, medical

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