Photothermal Effect Enhancing Nanozyme-mediated Tumor Catalytic Therapy

In recent years,catalytic therapy based on tumor microenvironment has become a promising anticancer strategy due to its specificity,high efficiency,and low toxicity.However,the further development of tumor catalytic therapy has been limited due to the low catalytic activity of nanozymes.In this paper,in order to improve the activity of nanozymes,develop a new and efficient nano-catalytic system,and realize efficient tumor catalytic therapy,the following studies have been carried out.1.First,according to the relationship between enzyme activity and temperature,a temperature-based nanozyme activity regulation system was designed.The system consisted of two parts,one is graphene quantum dots(GQDs)with peroxidase activity,and the other is semiconducting polymer nanoparticles(SPNs)with near-infrared photothermal properties.Under the irradiation of near-infrared laser,SPNs produced photodynamic and photothermal effects.The photothermal effect made the temperature rise to the optimal position,which fully stimulated the nanozyme activity of GQDs.The optical,enzymatic,and photothermal properties of the nanocomposite enzyme GQD-SPNs were verified by various experiments.2.After the successful preparation of GQD-SPNs nanocomposite,the in vitro anti-tumor effect of GQD-SPNs was investigated in the human cervical cancer cell line(HeLa).MTT experiments proved that GQD-SPNs can significantly inhibit the proliferation of HeLa cells and promote their apoptosis.Cell uptake experiments proved that GQD-SPNs can be efficiently endocytosed into HeLa cells to exert anti-tumor effects.Intracellular reactive oxygen species(ROS)assay confirmed the greatly improved intracellular ROS level from GQD-SPNs.3.The in vivo anti-tumor effect of GQD-SPNs was further verified on the HeLa tumor-bearing mice.In vivo fluorescence imaging verified the effectively accumulation of GQD-SPNs in tumor site.The fluorescence intensities of the tumor site reached highest values at 24 h after administration.Laser treatment has the best effect at this time point.Infrared thermal imaging verified the effectively photothermal conversion of GQD-SPNs and caused the tumor temperature increased.Afterwards,the treatment was taken on HeLa tumor-bearing mice for 16 days.The tumor volumes and body weights of mice were recorded,the results proved that GQD-SPNs have super anti-tumor effect and good biological safety.Tissue staining further confirmed the biological safety and therapeutic effect of GQD-SPNs.In summary,the multifunctional nanocomposite enzyme GQD-SPNs had excellent photodynamic and photothermal activity,which not only realized efficient phototherapy,but also greatly stimulated the nanozyme activity of the GQDs,leading to an efficient and enhanced catalytic treatment of tumors.The combination of phototherapy and catalytic therapy exerted a significant anti-cancer effect on HeLa tumor-bearing mice.The growth rate of tumors was significantly blocked and the survival time was significantly prolonged.