Smart nanoplatform based on mesoporous polydopamine for combined photothermal-chemotherapy in the treatment of urothelial carcinoma

NIR triggered PCM gatekeeper enables on demand release of erdafitinib and baicalein from MPDA nanoplatform • MPDA mediates photothermal ablation while erdafitinib provides chemotherapy for synergistic anti-tumor effect • Baicalein endows PMP@ED/Ba with potent non‑enzymatic antioxidant activity to alleviate oxidative stress • PMP@ED/Ba shows excellent biocompatibility and significantly suppresses tumor growth in vivo without major organ toxicity Urothelial carcinoma is a common urinary malignancy with high recurrence, easy progression to muscle-invasive disease, and resistance to conventional therapies. To address the clinical challenges of poor drug retention, low bioavailability, severe toxicity, and the inability of monotherapy to inhibit tumor recurrence and metastasis, a smart responsive nanoplatform (PMP@ED/Ba) based on mesoporous polydopamine (MPDA) was designed and constructed. This platform uses a thermosensitive phase-change material as a gatekeeper to co-load erdafitinib (FGFR inhibitor) and baicalein (antioxidant). Systematic characterizations confirmed the successful fabrication of the nanocomposite with uniform spherical morphology. Under 808   nm NIR irradiation, PMP@ED/Ba exhibited good concentration- and power-dependent heating and photothermal stability, with a photothermal conversion efficiency of 26.3%. The PCM gatekeeper enabled NIR triggered on-demand drug release, preventing premature leakage. DPPH/ABTS assays demonstrated potent non-enzymatic antioxidant activity, efficiently depleting ROS. Hemocompatibility and cytotoxicity tests confirmed good biocompatibility. In vitro and in vivo studies showed that PMP@ED/Ba plus NIR irradiation significantly suppressed T24 tumor growth through synergistic photothermal-chemotherapy, inducing extensive apoptosis and necrosis without major organ toxicity. This smart platform provides an efficient, low-toxicity strategy for locoregional treatment of urothelial carcinoma.