Supramolecular nanomedicines derived from phase-change materials coated with hyaluronic acid for multi-modality cancer therapy.

The treatment of malignant tumors such as melanoma has always been a world-class problem. Single-modality therapy for melanoma is often faced with a balance of therapeutic outcomes and side effects. Combination of multi-modality could greatly improve therapeutic effect without introducing side effects. Herein, the thermal responsive phase change materials (PCM) are utilized to incorporate ultrasmall copper sulfide nanoparticles (CuS NPs) and doxorubicin (DOX), which were furtherly coated with hyaluronic acid (HA) via strong host-guest interaction between β-cyclodextrin (CD) and ferrocene (Fc), for on-demand combined chemo, chemo-dynamic and photothermal therapy. The supramolecular nanomedicines could accumulate at tumor site owing to HA coating upon intravenous injection, and PCM would melt to release CuS NPs, DOX as well as Fc under NIR laser irradiation. Both in vitro and in vivo antitumor results have demonstrated the predominant effect of supramolecular nanomedicines, compared to DOX or CuS NPs, exhibiting better antitumor growth performances. These results highlight the promise of CuS-DOX@PCM-CD@HA-Fc in combining chemotherapy, chemo-dynamic therapy and photothermal combined therapy to overcome current limitations of cancer therapies.