Applied Research Of PEGylated Platinum Nanoparticles On Tumor Imaging And Combined Therapy

Cancer has been the primary threat to the human health.The rapidly developing nanotechnology provides powerful weapons for the diagnosis and therapy of malignancies.Noble metal nanomaterials represented by gold,silver and platinum group nanoparticles have been widely applied in in vivo imaging,biological detection,phototherapies and bacteriostasis due to their unique optical,electrical and catalytic properties as well as diversities of biological effects.The platinum nanoparticles are typical noble metal nanomaterials whose electrical and catalytic properties have been deeply investigated.And in the biomedical field,the nanoparticle has been utilized to enhance photothermal therapy and radiotherapy.However,the present applications of the platinum nanoparticles in tumor diagnosis and therapy are confined to a cellular context,which creates a huge gap between basic research and clinical translation.Based on the current research status,we prepare a biocompatible and biologically applicable platinum nanoparticles which are used for photoacoustic and CT imaging by virtue of their strong NIR light-thermal conversion and X-ray attenuation abilities.Meanwhile,by controlling the power of the laser,we relieve the hypoxia in the tumor region and augment the radiotherapy efficacy because of the mild hyperthermia.On the premise of lowered laser power and X-ray dose,the tumor growth is completely inhibited by the photothermal therapy in the NIR II window and nanoparticle-enhanced radiotherapy while the safety of the combined therapy is guaranteed.Additionally,we systematically evaluate on the toxicity of the platinum nanoparticles at the whole animal level,providing security data for supporting the clinical translation.The main findings of this dissertation are as follows:Chapter 1: Many applications of nanomaterials in the field of tumor imaging and therapy are briefly summarized.And the biological toxicities and mechanisms possibly caused by nanomaterials are also reviewed.The motivations and contents of our research in this dissertation are finally discussed.Chapter 2: The preparation and related characterizations of the PEGylated platinum nanoparticles are introduced.We synthesize the uniform and worm-like nanoparticles with high-temperature heating in an oil phase and modify their hydrophobic surface with an amphipathic polymer,18PMH-PEG,obtaining Pt-PEG nanoparticles with an appropriate size,good water solubility and stable dispersibility in physiological solutions.The preparation method is simple,facile and repeatable,providing solid foundation for the follow-up experiments and clinical translation.Chapter 3: The pharmacokinetic behavior and tumor imaging applications of the Pt-PEG nanoparticles are discussed.Benefiting from the excellent surface modification,Pt-PEG nanoparticles circulate in the blood for a long time and accumulate in the tumor region effectively.The dynamic accumulating process of nanoparticles in the mouse tumor is monitored by photoacoustic imaging in real time.Meanwhile,we prove the strong X-ray attenuation ability of the nanoparticles,which are utilized as a contrast agent for in vivo CT imaging.Chapter 4: PEGylated platinum nanoparticles for cancer therapy and their biological toxicities are presented.The Pt-PEG nanoparticles show high light-thermal conversion capacity in the second biological window while the nanoparticles can absorb X-ray and kill the surrounding cells.Hence we successfully realize in vitro photothermal and radio-sensitization therapy,respectively.On animals,we improve the tumor oxygen supply by mild photothermal heating and completely inhibit the tumor growth by nanoparticle-mediated radio-sensitization.We further systematically evaluate the bio-toxicities of the Pt-PEG nanoparticles,demonstrating the security of the nanoparticles applied in animals are long-term controllable.In summary,we prepare biocompatible platinum nanoparticles coated with PEG using a facile and repeatable method.The nanoparticles are successfully utilized for multimodal tumor imaging and photothermal therapy in the NIR II window in combination with radiotherapy,which paves a new way for the further investigations of the Pt nanoparticles and provides theoretical and experiment basises for the final clinical application.