Tumor cells are under siege from all sides: Tumor Cell-Mimic Metal−Organic framework nanoparticles triggering Cuproptosis/Ferroptosis/Apoptosis for Chemo-Chemodynamic-Photothermal-Immunological synergistic antitumor therapy

Combination therapy harnessing multiple cell death mechanisms has emerged as a promising approach for cancer treatment. However, the optimization of therapeutic synergies when integrating different modalities remained a challenge. In response, we have developed a multifunctional copper (Cu)-based metal–organic framework (MOF) nanoparticle loaded with mitoxantrone (MTO) and axitinib (AXB) incorporating tumor cell membrane (termed as M/A@MOF@CM) for synergistic cuproptosis/ferroptosis/apoptosis anticancer therapy. M/A@MOF@CM exhibited a diverse range of therapeutic activities, such as chemotherapy, photothermal therapy (PTT), and chemodynamic therapy (CDT), thereby enhancing immunogenic cell death (ICD) for potential immunotherapy. As a consequence, the comprehensive approach led to a substantial 86.45 % inhibition in primary tumor and a noteworthy 65.61 % suppression in distant tumors. This work constructs a multifunctional MOF nanoparticle, achieving "tumor cells are under siege from all sides", which potentially ushers in a new era in the realm of MOF-based synergistic cancer therapy platforms.