Enhanced targeting of prostate cancer-initiating cells by salinomycin-encapsulated lipid-PLGA nanoparticles linked with CD44 antibodies.

Abstract

Prostate cancer is the fifth most common cause of cancer-associated mortality in males worldwide. The survival of prostate cancer-initiating cells (CICs) is an important factor behind the metastasis and recurrence of prostate cancer. The cluster of differentiation (CD) 44 antigen is considered an important marker for prostate CICs. Salinomycin is a potent therapeutic drug against CICs. The present study demonstrated that salinomycin exerts potent activity against CD44+ prostate CICs. To further enhance this anticancer effect, salinomycin-encapsulated lipid-poly(lactic-co-glycolic acid) nanoparticles linked with CD44 antibodies (SM-LPN-CD44) were generated. The anticancer effect of the nanoparticles was investigated in a series of assays, including a cytotoxicity assay, flow cytometry and anticancer assay in prostate cancer-bearing mice in vivo. The results revealed that SM-LPN-CD44 could efficiently and specifically promote the delivery of salinomycin to CD44+ prostate CICs, and there by achieve greater inhibition of the cells compared with that achieved by salinomycin and non-targeted nanoparticles. To the best of our knowledge, this is the first study to report improved therapeutic effects against prostate CICs achieved by the enhancement of targeted drug delivery via nanoparticles conjugated with CD44 antibodies. Therefore, SM-LPN-CD44 nanoparticle-based therapy represents a novel approach to eliminate prostate CICs and is a promising potential treatment strategy for prostate cancer.