Work

Down‐Regulation of SOX2 Expression by pH‐Responsive Micelles Inhibits the Formation of Invadopodia in Prostate Cancer and Enhances the Effect of Chemotherapy

Year: 2025

Type: article

Abstract: ABSTRACT The incidence of prostate cancer in middle‐aged and elderly men is increasing year by year, and the existing drug treatment programs have limitations. In this study, a pH‐responsive micelle loaded with doxorubicin (DSPE‐PEG‐pronethalol‐DOX micelle nanoparticles, DOX@DSPE‐PEG_Prone) was prepared for the treatment of prostate cancer. The micelles were synthesized by esterification of SRY‐Box transcription factor 2 (SOX2) inhibitor pronethalol and DSPE‐PEG‐COOH, which could self‐assemble into micelles in water and encapsulate DOX. The characterization results show that DOX@DSPE‐PEG_Prone have good water solubility, stability, and drug loading, and exhibit charge reversal and rapid drug release characteristics in the tumor microenvironment. In vitro experiments showed that DOX@DSPE‐PEG_Prone could enhance the efficacy of DOX and effectively inhibit the proliferation and migration of prostate cancer cells. DOX@DSPE‐PEG_Prone successfully down‐regulated the expression of SOX2 in prostate cancer cells and inhibited the formation of invadopodia in prostate cancer cells. In vivo experiments showed that DOX@DSPE‐PEG_Prone could significantly inhibit the growth of subcutaneous tumors of prostate cancer without obvious organ toxicity. Overall, this study provides a potential drug delivery system for the treatment of prostate cancer.

Source: ChemistrySelect

DOI: 10.1002/slct.202501379