Preparation Of A Novel Photothermal Nanomaterials For Imaging-guided Photothermal Therapy

Photothermal therapy?PTT?,which has advantages including efficiency,minimal invasion,low toxicity comparing with the traditional cancer treatments such as surgery,radiation and chemotherapy,has attracted increasing attention recently.It employs photothermal agents to absorb near-infrared light and then convert it into the thermal energy so that the temperature at the tumor site rapidly increases over 48?,which can localize elimination of tumor cells.Therefore,the development and preparation of photothermal agents with high light-to-heat conversion efficiencies are crucial for promoting the development of photothermal therapy.In recent years,with the rapid development of nanotechnology,the development of photothermal conversion agents based on various nanomaterials has become a research hotspot in the field of photothermal therapy.Among them,semiconductor nanomaterials exhibit good application prospects due to their advantages of low cost,good biocompatibility and high light-to-heat conversion efficiency.In addition,apart from photothermal conversion agents,the implementation of successful photothermal therapy is inseparable from the assistance and guidance of molecular imaging technology in all stages of treatment.However,the single-function photothermal therapy is not synchronized with the diagnosis,and it is easy to delay the best treatment opportunity,resulting that it is very restricted in application.Therefore,the theranostics by providing the imaging function to the photothermal agent has become an effective way to significantly improve the therapeutic effect of the tumor.Against the shortcomings of the single-function photo-thermal agent,this study aims to develop a theranostic agent integrating imaging components and photo-thermotherapy.Two kinds of nanoagents for cancer diagnosis and treatment with high light-to-heat conversion efficiency were specifically designed and prepared,which can achieve the medical imaging-guided photothermal therapy of tumors.Therefore,this dissertation mainly includes:?1?preparation of urchin-like Mo-W₁₈O₄₉ and its application in tumor diagnosis and treatment;?2?preparation and functionalization of Cu₉S₅ nanocrystals and its application in tumor diagnosis and treatment.Details are as follows:1.By one-step solvothermal reaction,the hydrophilic urchin-like and spherical Mo-W₁₈O₄₉ probe with a size of about 1?m was successfully prepared.This oxygen-deficient tungsten oxide compound has high photo-thermal conversion efficiency.After two different morphological Mo-W₁₈O₄₉ probes were delivered to the tumor site by intratumoral injection,under the same experimental conditions of 808 nm laser irradiation,urchin-like Mo-W₁₈O₄₉ had better photothermic effects,which can be attributed to two aspects:?1?The urchin-like Mo-W₁₈O₄₉ has a higher photo-thermal conversion efficiency than the spherical Mo-W₁₈O₄₉;?2?Due to its special morphology,the urchin-like Mo-W₁₈O₄₉ is more likely to be enriched in the tumor site,thereby enhancing the effect of photothermal therapy.In addition,since the W element has a high X-ray absorption coefficient,the urchin-like Mo-W₁₈O₄₉ can be used as a contrast agent for CT imaging.Therefore,the probe can be used for CT imaging-guided tumor photothermal therapy.2.Preparation and application of tumor microenvironment-responsive OFF-ON probe Cu₉S₅-Cy5.5.By thermal injection method,Cu₉S₅ nanocrystals with a size of only 11 nm were successfully prepared,and using MUA,the water-soluble Cu₉S₅-MUA was synthesized by ligand exchange.It was found that under the same experimental conditions,the same concentration of Cu₉S₅ nanocrystalline solution heated faster than gold nanorods,indicating that it has a higher light-to-heat conversion efficiency.An off-on probe Cu₉S₅-Cy5.5 with response to tumor microenvironment was successfully prepared by disulfide bonding of Cu₉S₅ nanocrystals and near-infrared dye Cy5.5.Under normal physiological conditions,Cu₉S₅-Cy5.5 is quenched by fluorescence due to the fluorescence resonance energy transfer?FRET?effect;after 10 min of GSH treatment,the fluorescence gradually recovers and the intensity increases to 8.6 times,because in the presence of GSH,disulfide bonds were reduced and the fluorescence of Cy5.5 recovered.Finally,intratumoral injections were used to deliver the probes to the site of the tumor to achieve redox-responsive near-infrared fluorescence imaging-guided photothermal therapy,achieving very good therapeutic results.