Nanomedicines for prostate cancer therapy: stimuli-responsive design and disease-specific applications

Prostate cancer (PCa) remains a major malignancy among men and is clinically complicated by biological heterogeneity, treatment resistance and frequent bone metastasis. Current therapeutic strategies, including radical local treatment, androgen deprivation therapy, androgen receptor (AR) pathway inhibitors, chemotherapy and radioligand therapy, have improved disease control, but their efficacy is often limited by systemic toxicity, functional burden and insufficient tumour selectivity. Chemistry-enabled nanomedicines offer a versatile route to improve drug solubility, circulation, tumour accumulation and controlled therapeutic activation. In this review, we summarise recent advances in nanomedicines for PCa therapy with an emphasis on two closely related aspects: stimuli-responsive design and disease-specific applications. First, endogenous stimuli-responsive drug delivery systems are discussed, including platforms activated by acidic pH, hypoxia, redox imbalance and aberrant enzyme activity. Exogenous systems regulated by light, ultrasound and magnetic fields are then reviewed, with attention to how carrier architecture, responsive linkers, surface transformation and externally triggered activation influence payload release and therapeutic output. Second, PCa-specific nanoplatforms are highlighted, focusing on prostate-specific membrane antigen (PSMA)-directed delivery, AR axis- and castration-resistant prostate cancer (CRPC)-oriented intervention, and bone metastasis-adapted design. Nanomedicine-enabled combinations with immunotherapy or radiotherapy are also considered. Finally, we discuss key challenges related to tumour delivery efficiency, structural complexity, manufacturing reproducibility, biosafety and patient stratification. Overall, this review highlights how rational chemical design can be integrated with prostate cancer biology to develop more precise and clinically translatable nanotherapy strategies.