Drug resistance in castration-resistant prostate cancer and the therapeutic potential of mesoporous polydopamine-based nanoplatforms

In castration-resistant prostate cancer (CRPC), the benefit of androgen receptor signaling inhibitors, taxanes, poly(ADP-ribose) polymerase (PARP) inhibitors, and immunotherapy is limited by systemic toxicity, molecular heterogeneity, biomarker-restricted efficacy, and prior therapy cross-resistance. These limitations undermine long-term disease control, particularly when tumoral drug distribution, intracellular retention, or multi-agent co-delivery is suboptimal. This review outlines major resistance mechanisms and their impact on current systemic regimens. It then introduces mesoporous polydopamine (MPDA) as a versatile nanoplatform with high drug-loading capacity, facile surface functionalization, photothermal responsiveness, and compatibility with combinatorial regimens. Reported PC-3 experiments include approximately 53% cell death with AS1411-targeted MPDA/docetaxel plus irradiation versus 25% without irradiation, and representative Annexin V/propidium iodide double-positive fractions of 85.9% with irradiated MPDA-mediated docetaxel/small interfering RNA co-delivery versus 39.5% with free docetaxel.