Study Of Multifunctional Polypyrrole-based Nanomaterials In Synergistic Tumor Therapy

Cancer has become the leading cause of death in humans.In view of the fact that traditional cancer treatment methods cannot achieve safe and effective tumor treatment,it is still a huge challenge for clinicians and researchers all over the world to seek treatment strategies with satisfactory curative effects and fewer side effects.Among the new therapeutic methods,Photothermal therapy(PTT)has been widely studied because of its advantages of high spatial selectivity,noninvasiveness,and negligible drug resistance.In the process of PTT treatment,near-infrared light(NIR)is used as an external stimulus source,and photothermal agents(PTAs)convert the absorbed light energy into local heat to ablate cancer cells,which has been considered as a non-invasive Tumor-specific treatment.The development of multimodal therapy based on photothermal therapy is of great importance for the realization of effective tumor treatment.Due to the unique physiological characteristics of tumors,it is difficult to achieve the complete ablation of tumors by a single treatment mode.In this paper,an integrated multifunctional diagnosis and treatment nanoparticle based on polypyrrole nanoparticles was proposed and prepared.In this process,the pyrrole monomer is polymerized to form polypyrrole nanoparticles through the ferric chloride-mediated oxidation reaction,and then the surface of the nanoparticles is modified with graphene oxide(GO)sheets.The encapsulation of GO sheets not only facilitates the modification of po lyethylene glycol(PEG)to improve biocompatibility,but also provides active sites for the loading of gold nanoparticles and IR820 molecules.The obtained nanoparticles show good photoacoustic imaging(PAI)and CT imaging capabilities.Under near-infrared light irradiation,the nanoparticles can effectively generate hyperthermia and reactive oxygen radicals,consequently inducing photothermal therapy and photodynamic therapy.The loaded gold nanoparticles have catalase-like activity,which can catalyze the generation of oxygen from tumor site-overexpressed hydrogen peroxide,and enhance the effect of photodynamic therapy.Cell experiments have proved that the nanoparticles can effectively kill tumor cells through the synergistic effect of photothermal/photodynamic therapy.Ferroptosis is a promising form of programmed cell death,which eventually leads to cell death by producing excess intracellular lipid peroxide.Through Fenton reaction,ferrous ions can convert the low-toxic H₂O₂ into highly toxic hydroxyl radicals(·OH),effectively inducing ferroptosis.Based on this,we developed a multifunctional nanoreactor based on polypyrrole to achieve efficient synergistic treatment for malignant tumors through photothermal-induced apoptosis and Fenton reaction-induced ferroptosis.Firstly,polypyrrole nanoparticles were prepared by aqueous polymerization method,ferrous phosphate was grown in situ on the surface,and then glucose oxidase(GO x)was loaded.The nanoparticles can catalyze glycolysis at tumor sites,providing a lower p H environment and higher H₂O₂concentration for Fenton reaction.Thus,the production of·OH is promoted,inducing ferroptosis with high efficacy.After Fenton reaction,the generated ferric ions can consume the overexpressed glutathione(GSH)at the tumor site,further improving the therapeutic effect of ferroptosis.Under the irradiation of near-infrared light,hyperthermia can be generated to realize tumor cell apoptosis,which can promote the generation of free radicals.A series of in vivo and in vitro experiments have proved that the obtained nanoparticles can achieve synergistic treatment of tumors through photothermal-induced apoptosis/Fenton-induced ferroptosis.