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 language | English |
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Pages (from-to) | 2026-2032 |
Number of pages | 7 |
Journal | ACS Applied Bio Materials |
Volume | 4 |
Issue number | 3 |
DOIs | |
Publication status | Published - 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.
Keywords
- cancer
- doxorubicin
- drug delivery
- esterase
- fluorescence
- theranostic
ASJC Scopus subject areas
- General Chemistry
- Biomaterials
- Biomedical Engineering
- Biochemistry, medical