FZD7-Targeted Nanoparticles to Enhance Doxorubicin Treatment of Triple-Negative Breast Cancer.

Autor:	Hoover EC; Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States., Ruggiero OM; Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States., Swingler RN; Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States., Day ES; Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States.; Department of Materials Science and Engineering, University of Delaware, Newark, Delaware 19716, United States.; Helen F. Graham Cancer Center and Research Institute, Newark, Delaware 19713, United States.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2024 Mar 16; Vol. 9 (12), pp. 14323-14335. Date of Electronic Publication: 2024 Mar 16 (Print Publication: 2024).
DOI:	10.1021/acsomega.3c10275
Abstrakt:	Doxorubicin (DOX) is a chemotherapy agent commonly used to treat triple-negative breast cancer (TNBC), but it has insufficient efficacy against the disease and considerable toxicity due to its off-target delivery. To improve the specificity of DOX for TNBC, we encapsulated it in poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs) coated with antibodies against Frizzled7 (FZD7), a receptor that is overexpressed on TNBC cells and which is a key activator of the Wnt signaling pathway. In vitro studies show that DOX encapsulation does not hinder its ability to localize to the nucleus in human TNBC cell cultures and that DOX delivered via NPs induces apoptosis and DNA damage via H2A.X phosphorylation to the same degree as freely delivered DOX. FZD7-targeted NPs delivering DOX caused significantly greater inhibition of metabolic activity and led to a smaller cell population following treatment when compared to freely delivered DOX or DOX-loaded NPs coated only with poly(ethylene glycol) (PEG). The FZD7 antibodies additionally provided significant levels of Wnt pathway inhibition, as demonstrated by an increase in β-catenin phosphorylation, indicative of β-catenin destruction and downregulation. These results show that FZD7-targeted platforms have great promise for improving the therapeutic window of otherwise toxic chemotherapies like DOX in TNBC and other cancers that display the overexpression of FZD7 receptors. Competing Interests: The authors declare no competing financial interest. (© 2024 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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