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

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.