Preparation Of Nanomaterials Responsive To Near Infrared Light And Their Application In Tumor Diagnosis And Treatment

Cancer is one of the major diseases that endanger human health.So far,conventional treatment methods that used in clinical,like surgery,radiotherapy and chemotherapy are the most commonly,but there still are some drawbacks or deficiencies,such as low drug utilization rate,poor treatment effect,high cost,easy recurrence,and large side effects that can not be ignored.With the development of nanotechnology,nanomaterials are widely used in biomedical fields,such as drug delivery,biological imaging,disease diagnosis and treatment,which provide new opportunities for cancer treatment.The meticulous design and functional regulation of nanomaterials have greatly improved their structure,composition,physicochemical properties and application effects.It is of great clinical significance to develop multifunctional nanomaterials to realize early detection,early diagnosis and early treatment of cancer.In recent years,temporally and spatially controllable lighttriggered cancer therapy,namely phototherapy,has attracted extensive attention due to its good tumor selectivity and ideal therapeutic effect.In particular,the development of nanomaterials responsive to near-infrared light（700～1100 nm）to achieve effective tumor phototherapy has become a research hotspot in the field of light-controlled therapy.Based on this,we designed and synthesized a series of inorganic functional nanomaterials responsive to near-infrared light,and studied their physicochemical properties,biocompatibility,imaging detection performance and tumor killing effect through multi-angle and multi-methods.The specific content of graduation thesis is summarized as follows:1.We successfully synthesized poly（vinylpyrrolidone）（PVP）-protected ultrasmall Cu_1.2O nanoparticles（NPs）as theranostic nanoagents for magnetic resonance imaging（MRI）-guided photothermal therapy.Due to the good near-infrared absorption capability and photothermal conversion effect of Cu_1.2O NPs,the generated heat can be well used in ablating tumor tissue under the irradiation of nearInfrared（NIR）light laser.Cu_1.2O NPs contains Cu2+ions,which can be well applied for Ti-weighted magnetic resonance imaging（MRI）for evaluating therapeutic progress.In vitro and in vivo studies demonstrated that Cu_1.2O NPs could be used as multifunctional nanoagents for diagnosis and treatment of cancer,which carry out the precise MRI-guided photothermal therapy,and achieve high antitumor effects with low toxic side effects.The reported near-infrared light responsive Cu_1.2O NPs for photothermal tumor ablation will shine more lights on the future research consideration in Cu-based theranostic nanoplatforms.2.We reported an intelligent nanocomposite（UCC,UCNP@CeO₂/CuO）with cancer cell membrane camouflaging（mUCC）to achieve boosting reactive oxygen species（ROS）generation within cancer cells for synergistic PDT and CDT with enhanced treatment efficacy.Upconversion nanoparticles（UCNP）was constructed as the core to convert long-wavelength NIR light into UV-vis light and CeO₂/CuO heterostructure was anchored on UCNP by epitaxial growth approach without the assistance of any capping agents.The fabrication of n-type CeO₂/p-type CuO heterojunction photocatalyst realized highly efficient charge transfer and had the capability to harvest the emission light of UCNP,which greatly improved the photocatalytic activity and ROS generation under NIR laser irradiation.Importantly,UCC with two redox pairs（Ce（Ⅲ）/Ce（Ⅳ）and Cu（Ⅱ）/Cu（Ⅰ））offered great potential as Fenton-like agent for ·OH generation in tumor microenvironment（TME）featuring relatively high content of H2O₂.The constructed mUCC gave rise to tumor microenvironment regulation on two aspects,oxygen production and glutathione（GSH）depletion,which relieved the hypoxia condition and destroyed antioxidant capability of tumor cells.The ampliative ROS accumulation at cellular level induced cell death in apoptosis and ferroptosis manner upon the irradiation of NIR laser.Under the guidance of MRI and NIR fluorescence imaging,mUCC exhibited relatively long blood circulation,high tumor accumulation,and deep tumor penetration thanks to the cancer cell membrane camouflage.In brief,mUCC could ensure higher ROS generation efficiency by maximize utilization of the special communications between photons and electrons,and achieved improved antitumor efficiency by synergistic PDT and CDT.3.We constructed a self-propelled cascade therapeutic biocatalyst（USCGP,UCNPs@MSN@CeO₂-GOD/PEG-cRGDfK）for additive enhanced synergistic starvation/photodynamic anticancer therapy.The outer CeO₂ with catalase（CAT）-like activity was selected as a promising O₂-self generating material.Sufficient O₂producing in situ further accelerated the catalytic oxidation of glucose by catalytic reaction of the loaded glucose oxidase（GOD）and shut down nutrient supply to achieve starvation therapy.As a result,the depleting of glucose realizes the regeneration of H2O₂ and altered the cell environment to be more acidic,which improved the peroxidase（POD）-like activity of CeO₂ for highly toxic OH generation.In addition,under 808 nm laser excitation,upconversion nanoparticles（UCNP）in the core converted NIR light to UV emission to trigger the photocatalysis reactions of CeO₂ in the shell,breaking O₂ and H2O into·O₂^-and·OH to induce cancer apoptosis effectively.Notably,the modification with PEG-cRGDfK allowed USCGP to bind αv_β3 integrin-overexpressed tumor cells specifically to enhance the cancer targeting ability and increased the administered dose reached to tumor site.Additionally,USCGP with excellent X-ray attenuation coefficient could serve as contrast agent for real-time computer tomography（CT）imaging in monitoring treatment process.Both in vitro and in vivo experiments indicated that USCGP yields high-performance in antitumor treatment with synergistic therapeutic outcome.