Cancer cell membrane-camouflaged and H2O2-activatable nanocomposites for synergistic chemotherapy and two-photon photodynamic therapy against melanoma

Melanoma is one of the most aggressive and deadliest forms of skin cancer. Besides traditional medicinal techniques, the use of photodynamic therapy is receiving increasing attention as a complementary method. Despite recent advances in the field, the majority of compounds unselectively localize inside the organism and are excited with blue or ultraviolet light, limiting the application of this method to superficial tumors. To overcome these drawbacks, herein, the encapsulation of cyclometalated iridium(III) prodrugs into selenium nanoparticles, which were further camouflaged with cancer cell membranes, is reported. The nanocomposite readily dissociated upon exposure to hydrogen peroxide, triggering the release of the iridium complex, which acts as a photosensitizer, as well as methylquinone and selenium nanoparticles, which act as glutathione scavengers and chemotherapeutic reagents. The reduced intracellular glutathione levels enhance the sensitivity of the cancer cells for anticancer treatment. The cancer cell membrane-camouflaged nanoparticles showed improved selectivity, membrane permeability, and pharmacokinetic effect for cancerous cells. Upon two-photon excitation at 730 nm, the nanoparticles were able to identify as well as nearly fully eradicate a melanoma tumor inside a mouse model by synergistic chemotherapy and near-infrared photodynamic therapy.