Catalytic Enhanced Chemo-Photo Tumor Combination Therapy

Given the complexity of cancer,chemotherapy combined with phototherapy has been a feasible treatment for a long time.However,the combination chemotherapy/phototherapy based on the nano-platform still has some limitations,such as cell resistance and hypoxic properties of the tumor site,which will reduce the chemotherapy effect and photodynamic efficacy.A safe theranostic system with sufficient ROS-generating ability is very desirable.Nano-catalytic medicine aims to regulate the tumor microenvironment through in-situ catalytic reactions and induce cell apoptosis through the formation or transformation of reactive oxygen species.The development of nanocatalytic medicine is helpful to overcome the limitations of phototherapy and chemotherapy,and realize efficient synergistic treatment.In this paper,a nanocomposite based on cerium oxide nanoparticles is proposed for the safe and efficient treatment of tumors.The main contents are as follows:1.The preparation of the PEGylated polyaniline(PANI)coated Ce Ox@polyacrylic acid(PAA)nanoclusters.The particle size of PAA-Ce Ox is 5.72 nm and the Zeta potential is-35.21 m V.The particle size of PAA-Ce Ox@PANI is 52.26 nm and the Zeta potential is 17.98 m V.The particle size of CP is 54.63 nm,Zeta potential is 1.09 m V,and the valence ratio of cerium Ce⁺⁴?Ce⁺³=3.46.CP has the properties of catalase at p H=7.4 trigerred by NIR light.After being treated with 10 m M of H₂O₂ and irradiation,the ratio of Ce⁺⁴?Ce⁺³ drops to 0.58,showing acidic p H-dependent oxidase properties.2.Indocyanine green(ICG)and doxorubicin(DOX)were loaded on the PAA-Ce Ox@PANI-PEG by?-?stacking to abtain CPID.The load ratio of DOX and ICG in CPID is about 17.8%and 16.8%.The release of DOX is acidic p H-responsive and can be accelerated by irradiation and hydrogen peroxide.CPID has excellent photothermal effect and the temperature can reach 76.7?after irradiation by 808 nm laser for 5min.The catalytic effect of Ce Ox promotes CPID to produce more singlet oxygen generation.3.In vitro.After cultivation for 6 h,the cells can effectively internalize CPID.CPID is mainly located in neutral cytoplasm and has less drug release due to its neutral surface zeta potential.After irradiation,CPID exerts its catalase properties,which can effectively alleviate cell hypoxia.At the same time,the PANI layer is expanded and a lot of drugs are released.The negatively charged PAA-Ce Ox nanoparticles then enter the acid lysosome and exert the oxidase properties,which will increase the ROS.Cytotoxicity studies have shown that the survival rate of the CP group without light is above 80%,and 99.8%of cells in CPID group can be killed after irradiation.4.In vivo.Multimodal imaging shows that nanoparticles can effectively accumulated in tumor 24 h after tail vein injection.Long-term treatment shows PDT/PTT/CHT/CDT synergistic treatment has the best anti-tumor effect.H&E staining shows the good biological safety of CPID.