An intelligent NIR-responsive chelate copper-based anticancer nanoplatform for synergistic tumor targeted chemo-phototherapy

The chelate copper-based anticancer drug bleomycin (BLM) is usually believed to bind metal ions especially Cu(II) to generate the “activated BLM” for DNA cleavage. Herein, BLM and L-menthol (LM) co-loaded hollow mesoporous Cu2−xS nanoparticles (HMCu2−xS NPs) with surface folic acid (FA) modification were formulated to construct an intelligent NIR-responsive nanoplatform for synergistic tumor targeted chemo-phototherapy. With the tumor targeting ability of the folate receptor (FR)-positive, FA-HMCu2−xS/BLM/LM could pinpoint tumor cells efficiently. Under NIR irradiation, the versatile HMCu2−xS would be bound to exploit the merits of phototherapy (including PTT and PDT-like effects) for cancer treatment. Meanwhile, benefiting from the controllable “solid–liquid” (S–L) phase transition feature of LM as a gatekeeper, FA-HMCu2−xS/BLM/LM offered a platform for simultaneous NIR-mediated temperature-responsive BLM and copper ion release, which further initiated the generation of the “activated BLM”. As a matter of course, the remarkable synergistic combination of Cu-dependent chemo-phototherapy in vitro and in vivo by such a smart all-in-one drug delivery nanoplatform developed here provided information for advancing nanotherapy in biomedical fields.