Journal
DRUG DISCOVERY TODAY
Volume 27, Issue 2, Pages 436-455Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2021.09.020
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Funding
- Spanish Ministry of Economy, Industry, and Competitiveness [PID2019-106094RB-I00/]
- Basque Coun-try Government [IT907-16]
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In this review, the molecular pathways regulating P-gp and its involvement in DOX resistance are highlighted. The development of nanocarriers for co-delivery of DOX with anticancer compounds and genes is also discussed. Furthermore, the surface modification of nanocarriers to enhance selectivity towards cancer cells is explored.
P-glycoprotein (P-gp) is a drug efflux transporter that triggers doxorubicin (DOX) resistance. In this review, we highlight the molecular avenues regulating P-gp, such as Nrf2, HIF-1 alpha, miRNAs, and long noncoding (lnc)RNAs, to reveal their participation in DOX resistance. These antitumor compounds and genetic tools synergistically reduce P-gp expression. Furthermore, ATP depletion impairs P-gp activity to enhance the antitumor activity of DOX. Nanoarchitectures, including liposomes, micelles, polymeric nanoparticles (NPs), and solid lipid nanocarriers, have been developed for the co-delivery of DOX with anticancer compounds and genes enhancing DOX cytotoxicity. Surface modification of nanocarriers, for instance with hyaluronic acid (HA), can promote selectivity toward cancer cells. We discuss these aspects with a focus on P-gp expression and activity.
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