Four-component of Double-Layer Infinite Coordination Polymer Nanocomposites for Large Tumor Trimodal Therapy Via Multi High-Efficiency Synergies

Multimodal /components tumors synergistic therapy is a crucial approach for enhancing comprehensive efficacy. Our research has identified lots of high efficiency synergies among four suitable components, revealing combinations with remarkably low combination index (CI) values (10 -3 -10 -8 ). These combinations hold promise for large tumor powerful electrothermal-thermodynamic-multi-chemo trimodal therapy. To implement this approach, we developed four -component of double -layer infinite coordination polymer (ICP) nanocomposites, in which hypoxia-activated AQ4N and thermodynamic agent AIPH coordinated with Cu(II) to form initial layer of positively charged ICPs-l NPs, chemotherapeutic agents gossypol-hyaluronic acid (G -HA) and CA4 coordinated with Fe(III) to form out layer of negatively charged ICPs-2 NPs, then double -layer infinite coordination polymer nanocomposites (ICPs-1@ICPs-2 CNPs) were fabricated by electrostatic adsorption using ICPs-l NPs and ICPs-2 NPs. Cell experiments have extensively optimized the coordination combinations of the four components and the composition of the two layers. A programmable three -stage therapeutic procedure, assisted by a microelectrothermal needle (MEN), was developed. Under this procedure the resulting nanocomposites demonstrate the powerful trimodal comprehensive therapeutic outcomes for large tumors using lower components dosage, achieving a tumor inhibition rate nearly reaching 100 % and no recurrence for 60 days. This study offers remarkable potential for tumor multimodal /components synergistic therapy in future.