Fe₃O₄-based Multifunctional Nanoparticles Combined Fenton Reaction With Photothermal Effect For Antitumor Therapy

Cancer is one of the major threats to human health in the world today.Traditional clinical cancer therapeutics,including surgery,chemotherapy and radiation therapy,etc.,are not only completely directed against tumor cells,but also cause certain harm to normal cells or healthy tissues,resulting in serious side effects to patients.Therefore,there is an urgent need for a highly effective and low-toxic therapeutic strategy to improve the therapeutic effect.In recent years,with the rapid development of nanoscience and nanotechnology in the biomedical field,active oxygen species(ROS)mediated chemotherapy has attracted much attention as a novel and highly effective anticancer therapy.High concentrations of ROS in tumor cells,such as hydroxyl radicals(·OH),can cause irreversible and severe oxidative damage to lipid membranes,mitochondria,and nuclear DNA,leading to cell apoptosis.Fenton reaction is one of the effective way to increase the intracellular ROS level.It exploits Fe2+/3+ to catalyze H2O2 production by cellular metabolism to produce a highly toxic and strong oxidative OH that eventually leads to apoptosis.Iron ions can be released from Fe3O4 nanoparticles under acidic condition,so the released iron ions can induce Fenton reaction,resulting in cell apoptosis.In addition,photothermal therapy has gradually become a research hotspot in the field of cancer treatment.It has excellent properties such as low invasiveness,low side effects,and rapid recovery.Polypyrrole(PPy)is an organic conductive polymer has strong near-infrared light absorption and excellent biocompatibility.Therefore,it can be used for photothermal therapy of tumors.Herein,we synthesized monodispersed small-sized magnetic Fe3O4 nanoparticles by solvothermal reaction.The in situ oxidative polymerization was used to polymerize polypyrrole with photothermal action on the surface of Fe3O4 nanoparticles.Then,the water solubility of the particles was improved with polyethylene glycol.In vitro and in vivo experiments.show that Fe3O4@PPy-PEG nanoparticles not only have significant photothermal effects to ablate tumor cells,but also can promote the release of iron ions from Fe3O4 to catalyze H2O2 into more OH to induce tumor cells apoptosis.In addition,the prepared Fe3O4@PPy-PEG nanoparticle also has good biocompatibility and better magnetic targeting to enhance the aggregation of particles in the tumor site,and can also perform magnetic resonance imaging.Therefore,our synthetic Fe3O4@PPy-PEG nanoparticles can be used as a new type of tumor therapy agent combined with Fenton-photothermal and magnetic resonance imaging.