Intelligent responsive copper-diethyldithiocarbamate-based multifunctional nanomedicine for photothermal-augmented synergistic cancer therapy

Abstract

The design of multifunctional nanomedicine through the combination of multimodal treatments to achieve the optimal antitumor effect is essential for cancer therapy. Herein, we design and develop a multifunctional theranostic nanoplatform using an iron ion-doxorubicin (DOX) nanoscale coordination polymer (Fe/DOX NCP) as a shell coating on the surface of polyvinyl pyrrolidone (PVP) stabilized copper-diethyldithiocarbamate nanoparticles (Cu(DDC)₂ NPs) for combined tumor chemo-/photothermal/chemodynamic therapy. The obtained Cu(DDC)₂@Fe/DOX NPs display pH/laser dual-responsive degradation behavior and also exhibit favorable photothermal performance. Under 808 nm laser irradiation, Cu(DDC)₂@Fe/DOX NPs can convert light into heat, which not only kills tumor cells via hyperthermia in photothermal therapy (PTT), but also accelerates the degradation of Fe/DOX NCPs to release Fe³⁺ and DOX. The liberated Fe³⁺ can be used to catalyze hydrogen peroxide via the Fenton reaction to produce highly toxic hydroxyl radicals (˙OH) in chemodynamic therapy (CDT). The released DOX and the exposed Cu(DDC)₂ can cause significant cell death in combined chemotherapy via a superimposed effect. In vitro and in vivo results prove that Cu(DDC)₂@Fe/DOX NPs with laser irradiation present remarkable anticancer performances in hyperthermia-enhanced chemo-/CDT. Therefore, this study provides a new strategy for highly efficient synergistic cancer therapy.