Multi-Mode Theranostics Based On Gold-Platinum Nanocomposite For Photothermal-Photodynamic Combined Tumor Therapy

In recent years,people have paid great attention to the treatment of tumors by photo-triggered therapy,which is due to the fact that light is easy to be focused and easily regulated,marking the localized treatment with accurate non-mvasive,and direct characteristics.However,single light therapy can not completely treat tumor,which leads to the failure of tumor treatment.For example,single photothermal therapy in the process of tumor treatment is uneven heat in all parts of the tumor,there is a problem of incomplete treatment.Photodynamic therapy(PDT),which uses reactive oxygen species(ROS)to kill tumor cells,is widely used in tumor therapy,and the hypoxia of most solid tumors severely limits the efficiency of PDT.At the same time,the hydrophobicity and limited tumor selectivity of some photosensitizers also reduced their PDT effect.The development of different functional materials can integrate different treatment models into a unified treatment platform to achieve synergistic treatment of tumors to enhance the efficacy of treatment.Using nanomaterials as therapeutic agents or cariers can not only improve the precision of treatment,but also greatly reduce the toxicity to healthy tissues in vivo.Due to the catalytic properties of some precious metal nanomaterials,the excess hydrogen peroxide in tumor tissue can be consumed to produce the oxygen-enhanced photodynamic therapy effect which is necessary in the course of photodynamic therapy.In addition,some noble metal nanomaterials exhibit excellent photothermal conversion properties due to their strong surface plasmon resonance effect,thus eliminating tumors at high temperature.The multi-functional cooperative therapy with nano-materials as carrier has been paid greatly attention.Although precious metal nanomaterials show excellent therapeutic effect in the field of tumor treatment,how to integrate all kinds of functional precious metal materials and give full play to the performance of nano-coordination has been the focus of research.The purpose of this paper is to develop a multifunctional gold-platinum multimodal nanodiagnosis and treatment probe to realize photothermal-photodynamic synergistic therapy of tumors.In the preparation of nanomaterials,Two kinds of nanomaterials,Au@Se and Au@TA,were modified by PAH to change the charge of the material,and then the photosensitizer Ce6 was connected by electrostatic adsorption to obtain Au@Se@Pt-Ce6 and Au@TA/Pt-Ce6 nanocomposite probes.The specific work is as follows:1.The Au@Se particles with strong absorption core-shell structure were synthesized by using nano-selenium coated gold nanoparticles,and the Pt layer was formed by in-situ reduction of Pt'+i the outer layer of the nanoparticles,and the thermal stability was excellent Au@Se@Pt nanomaterials with catalytic hydrogen peroxide performance were used to change the electrical properties of nanoparticles by using positively chaged PAH,and the photosensitizer Ce6 was modified to the nanomaterials to obtain Au@Se@Pt-Ce6 nanocomposite probes.The photothernal conversion efficiency,ROS formation,photoacoustic imaging,cytotoxicity and photofateality of Au@Se@Pt-Ce6 nanocomposite probe were studied.Finally,the photoacoustic imaging and phototihermal photodynaimc therapy of the nanocomposite probe in mice were studied by using HeLa nude mice model.The results show that the nanocomposite probe has excellent photoacousic imaging and phototheramal-photodynamic combined therapy.2.Gold@tannic acid nanoparticles(Au@TA)with strong absorption in near infrared were obtained by reducing chloroauric acid with tannic acid.Then Pt was complexed to the surface of gold@tannic acid nanoparticles to obtain Au@TA/Pt nanomaterials with catalytic performance of hydrogen peroxide.Then the positively charged PAH was used to change the electrical properties of the nanaparticles and the photosensitizer Ce6 was modified to the nanomaterials to obtain the Au@TA/Pt-Ce6 nanocomposite probe.We studied the photothermal conversion properties,ROS formation,photoacoustic imaging effect,cytotoxicity and cytotoxicity of Au@TA/Pt-Ce6 nanocomposite probes.Finally,the photoacoustic imaging and photothernal photodynamic therapy of the nanocomposite probe in HeLa nude mice were studied.The results show that Au@TA/Pt-Ce6 nanocomposite probe has excellent photoacoustic imaging and photothermal-photodynamic effect.