Preparation Of Platinum-Iron Composite Nanomaterials And Their Application In Synergistic Tumor Therapy

As one of the major threats to human health,cancer has seen a significant increase in morbidity and mortality in rec ent years.Among the many cancer treatment methods,the studies revealed that almost all of the noninvasive therapeutic approaches such as chemotherapy,radiotherapy（RT）,photo-dynamic therapy（PDT）,sonodynamic therapy（SDT）and chemodynamic therapy（CDT）were involved in boosting the intracellular oxidative stress via the overgeneration of reactive oxygen species（ROS）to disarrange the redox homeostasis and induce cancer cell death.Nevertheless,tumor cells are extremely tolerant to the increased intra cellular ROS via developing profitable pathways for producing antioxidants such as glutathione and improving the activity of enzymes including catalase and glutathione peroxidase to regulate the balance of redox homeostasis.However,a single treatment met hod cannot completely solve the problem of tumor suppression and metastasis.T herefore,multimodal combination therapy is more likely to become a way of tumor treatment.In this paper,a cancer cell membrane-camouflaged nanohybrid,namely CaO₂@Fe Pt-DOX@PDA@CM（CFDPM）,was prepared by integrating calcium peroxide（CaO₂）,platinum iron nanoparticles（Fe Pt NPs）,doxorubicin（DOX）,polydopamine（PDA）and 4T1 cell membranes（CM）and developed for synergistic chemotherapy/chemodynamic therapy/Ca²⁺overloading-mediated amplification of tumor oxidative stress and photothermal enhanced cancer therapy.Camouflage of the4T1 cell membrane enabled CFDPM to escape the immune surveillance and accumulate in the tumor tissue.In T ME,owing to the degradation of CaO ₂in CFDPM,abundant Ca²⁺,O₂,and H₂O₂ were generated,which were beneficial for the subsequent synergistic bioreaction.Firstly,the Ca²⁺overloading would induce the mitochondrial dysfunction and promote the generation of ROS to result in the upregulation of oxidative stress in the tumor site.Secondly,the augmented H₂O₂level would be catalyzed into plentiful·OH by Fe Pt NPs,which could not only enhance the CDT effect but also further accelerate mitochondrial Ca²⁺aggregation due to the amplification of intracellular oxidative stress,which would further aggravate the cancer cell apoptosis.Finally,the generation of O ₂ would relieve the hypoxia condition of the tumor tremendously,which was beneficial for overcoming hypoxia-induced chemoresistance to strengthe n the chemotherapy effect.In addition,the excellent photothermal conversion property of CFDPM could further amplify the antitumor ability of PTT and PTT-induced promotion of CDT efficiency.T he in vitro and in vivo antitumor results confirmed that CFDPM provided a powerful synergistic therapeutic effect of chemotherapy,PTT,CDT,and disturbance of mitochondrial Ca²⁺homeostasis.T he studies revealed that CFDPM could effectively advance the therapeutic efficiency via the cooperation of various therapeutic modalities to optimize their individual virtue,which would open a valuable avenue for effective cancer treatment.