Core-satellite porphyrinic MOF@CuS nanoconstructs for combined chemodynamic/photodynamic/photothermal therapy

Combined therapy has attracted extensive attention as a potential solution to overcome tumor heterogeneity and drug resistance. However, developing simple and effective multifunctional therapeutic platforms remain to be further explored. Herein, we have constructed a hybrid nanoplatform composed of a hierarchically porous porphyrinic coordination network (HP-PCN) as the core and copper sulfide (CuS) nanoparticles (NPs) as the satellites to realize combined chemodynamic therapy (CDT)/photodynamic therapy (PDT)/photothermal therapy (PTT) of cancer. HP-PCN exhibits excellent photodynamic properties but its antitumor effect is limited by the insufficient penetration depth of laser and hypoxic tumor microenvironment (TME). To overcome the shortcomings of photodynamic monotherapy, we introduce negatively charged CuS NPs on the HP-PCN surface taking advantage of its porous structure and positive surface charge to fabricate core-satellite HP-PCN@CuS nanoplatform. CuS NPs have excellent photothermal performances and additional CDT function by reacting with hydrogen peroxide in the TME. The integration of HP-PCN and CuS NPs enables the hybrid nanosystem more potent antitumor efficiency. In vitro and in vivo experiments have shown that HP-PCN@CuS presents an combined CDT/PDT/PTT effect to significantly inhibit tumor growth with low systemic toxicity. This study provides a promising strategy to fabricate multifunctional therapeutic nanoplatforms for effective and combined antitumor applications.