Synthesis of RGD-dextran-coated Fe-porphyrin-based Zr-MOF for CT/MR imaging and targeted chemo-photothermal therapy of melanoma.

In the current study, a nanoscale metal-organic framework (MOF), FeP-Zr MOF, was synthesized with a Zr4+ metal core and Fe-porphyrin as connector ligands. Fe-porphyrin offers the MOFs a potent T1/T2-weighted magnetic resonance imaging (MRI) contrast for monitoring and high photothermal conversion for photothermal therapy (PTT). The highlight is that Zr metal nodes in the MOF structure could act as computed tomography (CT) imaging contrast agents. On the other hand, the porous structure of the MOF was utilized as a reservoir for loading doxorubicin (DOX). Then, the DOX-loaded MOF was surface-modified with dextran (DEX) and a linear cysteine-extended RGD peptide (cys-RGD) to improve biocompatibility and the therapeutic index against melanoma. The prepared platform showed a favorable conversion of 808 nm laser irradiation into heat. An in vitro study on B16F0 cells confirmed the targeted delivery of DOX to cancerous cells and also demonstrated the synergistic effect of 808 nm laser irradiation and DOX exposure on cellular toxicity. In the preclinical stage, after intravenous injection of the prepared platform into subcutaneous B16F0-tumor-bearing mice, it demonstrated efficient tumor accumulation, as visualized by MR and CT images. Furthermore, mice treated with DOX@FeP-Zr/DEX/RGD, along with 808 nm laser irradiation, showed 100 % tumor suppression. The current investigation introduces an innovative multipurpose platform for synergistic chemo-photothermal therapy (CPTT) of melanoma, offering dual-modal CT/MR imaging capabilities.