Diethyldithiocarbamate copper nanoparticle overcomes resistance in cancer therapy without inhibiting P-glycoprotein.

Autor: Kang X; Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA; Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA., Wang J; Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA., Huang CH; Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA., Wibowo FS; Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA., Amin R; Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA., Chen P; Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA., Li F; Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA; National Institute on Drug Abuse, National Institutes of Health, North Bethesda, MD 20852, USA. Electronic address: lif10@nih.gov.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2023 Jan; Vol. 47, pp. 102620. Date of Electronic Publication: 2022 Oct 18.
DOI: 10.1016/j.nano.2022.102620
Abstrakt: Copper diethyldithiocarbamate [Cu(DDC) 2 ] is a promising anticancer agent. However, its poor water solubility is a significant obstacle to clinical application. In previous studies, we developed a stabilized metal ion ligand complex (SMILE) method to prepare Cu(DDC) 2 nanoparticle (NP) to address the drug delivery challenge. In the current study, we investigate the use of Cu(DDC) 2 NP for treating P-glycoprotein (P-gp) mediated drug-resistant cancers. We tested its anticancer efficacy with extensive in vitro cell-based assays and in vivo xenograft tumor model. We also explored the mechanism of overcoming drug resistance by Cu(DDC) 2 NP. Our results indicate that Cu(DDC) 2 NP is not a substrate of P-gp and thus can avoid P-gp mediated drug efflux. Further, the Cu(DDC) 2 NP does not inhibit the activity or the expression of P-gp.
Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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