Multifunctional metal-polyphenol nanocomposite for melanoma targeted photo/chemodynamic synergistic therapy

Due to the hypoxic state of the tumor microenvironment (TME), photodynamic therapy (PDT) suffers from insufficient ROS production. The metal-polyphenol network-mediated Fenton reaction can generate reactive oxygen species (ROS) by consuming H2O2 in TME, improving the inadequate ROS generation problem of PDT. Therefore, synergistic therapy combining PDT and Fenton response-based CDT is a promising approach for cancer treatment. Herein, a metal-polyphenol nanocomposite was deposited with gallic acid grafted hyaluronic acid and Fe3+ to contrast a Ce6 nano-delivery system (Ce6@HSF NPs) for melanoma synergistic therapy. Ce6@HSF NPs could be used as a Fenton reagent to induce the ·OH production and enhance the PDT effect of Ce6 to a certain extent. After 4 h of cellular uptake, the fluorescence intensity of Ce6 in the Ce6@HSF NPs group was higher than 3 times that in the Ce6 group. The intracellular ROS generation level of the Ce6@HSF NPs (L) group combining CDT and PDT was higher than that of the Ce6 group and Ce6@HSF NPs group. In vitro and in vivo anti-melanoma studies show that Ce6@HSF NPs (L) group exhibited better anti-melanoma than other groups. Together, Ce6@HSF NPs provide a promising synergistic treatment potential for melanoma.