Synergistic therapy for melanoma via bioactive compounds derived metal-phenolic networks

Chemodynamic therapy (CDT) and photothermal therapy (PTT) are important adjunctive therapeutic approaches for tumors, complementing conventional methods like chemotherapy and radiotherapy. They play a crucial role in inhibiting tumor proliferation and metastasis. In this study, we established a combinational therapy strategy involving PTT and CDT for in situ and metastatic melanoma in experimental murine models. As-prepared S@M−EF system incorporated EGCG, a bioactive natural compound, known for its anti-tumor properties, which coordinated with FeIII to form an acidity-sensitive metal–organic framework (MPN). Sorafenib (SRF) was loaded in the system and released in the tumor microenvironment to work synergistically with FeIII and enhance the ferroptosis effect. Mesoporous polydopamine (MPDA) components inside S@M−EF exhibited photothermal characteristics. We conducted systematic in vitro and in vivo studies to assess the specificity and therapeutic effect of various S@M conjugates. Cellular examination confirmed that tumor cell ferroptosis could be induced and temperature could be increased due to photothermal conversion, and these two effects reinforced with each other. S@M−EF induced higher cell apoptosis compared to single functionalized conjugates (S@M, SRF, or M−EF). Enhanced therapeutic efficacy in melanoma and its metastasis was confirmed in murine models. This tumor microenvironment-responsive nanoplatform, based on natural molecules, combined CDT and PTT, offering a mutually enhanced treatment method for inhibiting tumor proliferation and metastasis.