High AIPH-Loaded Infinite coordination Polymers nanoparticles for long-term thermodynamic-chemo cascade tumor synergistic therapy

To enhance the tumor thermodynamic-chemo synergistic therapy efficacy, high loading of AIPH-Cu(II)-AQ4N Infinite Coordination Polymer nanoparticles (ICP NPs) were developed, which have high AIPH loading of 44.5 %, thermal stability, pH responsive release all therapeutic agents in the tumor tissue and lower toxicity. A long-term thermodynamic-chemo cascade tumor synergistic therapy strategy was developed with these nanoparticles. It is found ICP NPs exhibit diameters of 115.8 ± 23.7 nm, a substantial fraction of AQ4N and less 40 % of AIPH is released from ICP NPs within 70 h at pH 4.0–5.0, while the release rates of AQ4N and AIPH from ICP NPs over 72 h almost no release in normal tissues. A long-term two-stage therapeutic cascade procedure assisted by electrothermal was carried out, in which sufficient amount of AIPH maintain thermodynamic therapy 10 min at first stage and thermodynamic-chemo synergistic therapy 72 h at second stage. Under this procedure, the resulting nanoparticles demonstrate the powerful comprehensive therapeutic outcomes, small tumor entire eliminated and there is no recurrence for 60 days. Even for large tumors, the tumor inhibition rate is as high as 90 % at 16 days using lower drug dosage. This study offers remarkable potential for tumor cascade synergistic therapy in future.