Multifunctional PVA Microspheres For MRI-mediated Synergistic Treatment Of Tumor Embolization

Transcatheter arterial embolization(TAE)is an important method for the treatment of advanced liver cancer.The embolization material is injected into the supplying artery of liver cancer by transcatheter or intravenous catheter to block the blood vessels and interrupt the blood supply,so as to achieve the purpose of tumor treatment.However,only with TAE,postoperative tumor recurrence rate is high and it is difficult to monitor the therapeutic effect.Based on the good delivery function of polyvinyl alcohol(PVA),this paper developed two integrated diagnosis and treatment platforms for the embolization treatment of advanced liver cancer.Part I:PVA microspheres loaded with mitoxantrone are used in MRI mediated tumor embolization/photothermal/chemodynamic synergistic therapy.The chemotherapeutic drug mitoxantrone(MIT)coated with PVA constituted the microspheres.Polypyrrole(PPy)and ferric oxide(Fe₃O₄)were loaded on the surface of the microspheres.The embolic microspheres integrated with diagnosis and treatment of MIT@PVA@PPy@Fe₃O₄were constructed.In this platform,Fe₃O₄ has MRI contrast effect and can monitor the tumer treatment efficacy.In addition,the platform not only has the function of embolization therapy,but also the loaded PPy can be used for photothermal therapy,Fe₃O₄ can be used for chemical kinetics therapy,and MIT can be used for chemotherapy,realizing multi-mode collaborative therapy and overcoming the defects of single therapy.The experimental results show that the multi-mode collaborative therapy based on the platform can inhibit the growth of tumor cells and significantly improve the tumer treatment efficacy.Part II:Luteolin-Fe(LUT-Fe)loaded PVA microspheres for MRI-mediated tumor embolization/sonodynamic/chemodynamic synergistic therapy.LUT-Fe@PVA integrated diagnosis and treatment microspheres were constructed by using LUt-Fe polyphenol metal complexes loaded with PVA.The microsphere not only has the function of embolization,but also has MRI contrast performance and acoustic dynamic and chemical dynamic therapy effect with LUT-Fe loaded.The experiment results showed that LUT-Fe@PVA diagnosis and treatment integrated microspheres could not only produce hydroxyl radical(·OH)for CDT with endogenous overexpressed H₂O₂ of tumor,but also produce more cytotoxic ROS to kill tumor cells under the synergistic effect of ultrasound,thus further improving the therapeutic effect.This study shows that multi-functional diagnosis and treatment integrated PVA microspheres can not only make embolic microspheres visible,but also load different reagents to realize multi-mode collaborative treatment,further improve the treatment effect,and provide a new reagent and idea for the treatment of liver cancer embolization.