Construction And Application Of Transition Metal-based Nanomaterials For Tumor Synergistic Therapy

Despite cancer therapy has made significant improvements with the development of nanotechnology,cancer-relevant deaths remain a serious threat to human health globally due to the diversity,complexity,and heterogeneity of tumors.Encouragingly,recent decades have witnessed the forward exploitation and adhibition of technologies conceived for oncotherapy,some new cancer therapies have emerged such as photothermal therapy(PTT),photodynamic therapy(PDT),and chemodynamic therapy(CDT)etc.These methods use photothermal reagents,photosensitizers or catalysts to generate heat or reactive oxygen species(ROS)to kill cancer cells,which sufficiently inhibit tumor growth to a certain extent and prolong patient survival time gaining extensive attention among the research community currently.More precisely,PTT relies on heat produced by photoabsorbing agents to induce thermal ablation of cancer cells,and CDT utilizes in-situ Fenton or Fenton-like reaction to produce reactive oxygen species(ROS)to kill cancer cells.Nevertheless,monotherapies are normally insufficient to induce adequate tumor cell apoptosis.The combination of two or more therapeutic stratagems in one system has gained extensive attention due to a robust synergistic potentiation action with reduced toxic side effects.In summary,we combine PTT and CDT treatment strategies to build a multifunctional nanobiological platform to achieve PTT/CDT synergy for tumor ablation in this article.The details of research are addressed as follows:(1)First,bimetallic Mo/Fe-doped carbon nanoparticles(MoFe-CNPs)is fabricated via a simple one-step method.The MoFe-CNPs can not only be utilized as Fenton agents to convert the endogenous low-toxic hydrogen peroxide(H2O2)of tumor cells into highly toxic hydroxyl radicals(·OH)for CDT and simultaneously deplete glutathione for an amplified CDT effect,but also can be used as PTT agents to absorb near-infrared light(808 nm)to generate heat for PTT,and the resulting hyperthermia can further enhance the CDT effect.The hyperthermia induced by PTT can further enhance the CDT effect,achieving a synergistic PTT/CDT effect.More importantly,MoFe-CNPs enables effective destruction of tumors without inducing noticeable damage to normal tissues under 808 nm laser irradiation.The work presents a new type of multifunctional agent with high PTT/CDT efficacy,providing promising methods for tumor therapy.(2)Secondly,the self-assembled Cu/Mo nanoclusters(CuMoOx)under acidic conditions of tumors,which can aggregate into larger-sized nanoclusters under acidic conditions,showing good photothermal conversion ability(36.2 %).Also,CuMoOx can be used as a chemodynamic therapy(CDT)reagent to effectively catalyze the decomposition of H2O2 and produce hydroxyl radical(·OH).At the same time,the consumption of glutathione will also enhance the CDT effect.In vivo anti-tumor experiment demonstrates that the CuMoOx is able to effectively inhibit the tumor growth with minimal side effects.Generally speaking,these results indicate that the CuMoOx has huge potential for PTT/CDT synergistic cancer therapy.