Construction of Rough Surfaces Based on Zirconium Metal–Organic Frameworks to Enhance Photothermal and Photodynamic Therapy for Multiple Myeloma

Nanotargeted drug delivery systems (nanotargeted DDS) have emerged as promising solutions to improve treatment precision and reduce toxicity. However, achieving efficient delivery from the bloodstream to the tumor site remains challenging due to the complex tumor microenvironment (TME). To address these issues, a novel pH-responsive surface-switching DDS, UiO@CeO2/IR@(bPEI/HA)-A6, was designed. This system features CeO2 immobilized on zirconium metal-organic frameworks (UiO-66-NH2) to create a rough surface, which is then further modified with bPEI and HA-A6 polymers, facilitating its transport in the blood. After loading the photosensitizer IR-820, its photothermal conversion efficiency reached 26.8%, enabling effective photothermal and photodynamic therapy. The HA-A6 polymer enhanced the targeting effect through receptor-mediated recognition, ensuring more drug accumulation at the tumor site; the rough surface constructed by CeO2 increased cell uptake and enhanced endocytosis in cells. The acidic TME exfoliates the coating, exposing the rough surface of CeO2, which marked enhances the cellular uptake of DDS, thereby laying a solid foundation for DDS to play an antitumor role. These results indicate that UiO@CeO2/IR@(bPEI/HA)-A6 has excellent potential in the treatment of multiple myeloma.