A Tailored Multifunctional Anticancer Nanodelivery System for Ruthenium-Based Photosensitizers: Tumor Microenvironment Adaption and Remodeling.

Ruthenium complexes are promising photosensitizers (PSs), but their clinical applications have many limitations. Here, a multifunctional nano-platform formed by platinum-decorated and cyclodextrin ()-modified polydopamine () nanoparticles (NPs) loaded with a ferrocene-appended ruthenium complex () is reported. The NPs can successfully deliver to the tumor sites. The release of from the NPs can be triggered by low pH, photothermal heating, and HO. The combined photodynamic and photothermal therapy (PDT-PTT) mediated by NPs can overcome the hypoxic environment of tumors from several aspects. First, the platinum NPs can catalyze HO to produce O. Second, vasodilation caused by photothermal heating can sustain the oxygen supplement. Third, PDT exerted by can also occur through the non-oxygen-dependent Fenton reaction. Due to the presence of , platinum NPs, and , the nanosystem can be used in multimodal imaging including photothermal, photoacoustic, and computed tomography imaging. The NPs can be excited by the near-infrared two-photon light source. Moreover, the combined treatment can improve the tumor microenvironments to obtain an optimized combined therapeutic effect. In summary, this study presents a tumor-microenvironment-adaptive strategy to optimize the potential of ruthenium complexes as PSs from multiple aspects.