Synthesis And Characterization Of Multifunctional Noble Metal-Based Nanomaterials And Their Applications In Biological Detection And Therapy

With the development of nanoscience,many nanomaterials with excellent biological functions have been developed,which has led to their research and application in the field of biomedicine.Nanobiomedicine is an emerging discipline that applies nanomaterials to biomedicine,and controllable preparation of nanomaterials is the basis for the development of nanobiomedicine.Based on the two themes of biomedical diagnosis and treatment,designing and synthesizing functional nanomaterials to achieve portable and highly sensitive detection of disease markers as well as efficient treatment of lesions is particularly important.Noble metal nanomaterials have shown broad application prospects and huge application potential in energy,catalysis,biology,sensing,and medicine due to their unique physical and chemical properties.Generally,the noble metal nanomaterials are expensive and their applications are limited.Therefore,people began to focus on the development and application of noble metal-based nanocomposites.As a common biological dye,methylene blue?MB?has good visible light absorption capacity,photosensitive performance and light-to-heat conversion performance.The study found that MB as an excellent functional ligand is easy to coordinate with metal ions.Moreover,as a green and convenient method for the preparation of nanomaterials,photochemical synthesis has attracted the attention of researchers,but such method still has certain challenges in the realization of controllable preparation of nanomaterials.In this thesis,multifunctional noble metal-based nanomaterials were designed and synthesized using photochemical methods,and their applications in biological detection and treatment were explored.The specific works are as follows:1.We developed folic acid?FA?-modified two-dimensional Au nanosheets?FA-AuNSs?for specific recognition and sensitive detection of cancer cells.The AuNSs with well-tuned thickness were synthesized by using MB and photoinduced MB radicals as surface confining agent and reducing agent,respectively.The resulting nanosheets exhibited highly efficient catalytic activity during H₂O₂ decomposition to generate O₂,producing an obvious pressure increase in the detection system that can be detected by portable pressure meter.Therefore,FA-AuNSs could act as a highly selective and sensitive biosensor for pressure-based detection toward folate receptor-positive cancer cells with the detection limit of 50 cells mL^-1.Moreover,this pressure signal-based sensing strategy could also be used to detect cancer cells in serum samples,exhibiting potential clinical application.2.We designed two-dimensional Pd?II?methylene blue coordination polymers nanosheets?PdMBCPsNSs?for highly sensitive photothermal detection of H₂S biomarker molecule.The sensing mechanism is based on the decomposing effect of H₂S on PdMBCPsNSs,accompanied by the decrease of PdMBCPsNSs concentration and the increase of MB concentration.After adding H₂S,the heat released by PdMBCPsNSs under 808 nm laser irradiation decreased,while the heat released by MB under 650 nm laser irradiation increased.Such temperature change signals could be easily detected by a portable thermometer.The PdMBCPsNSs showed a highly sensitive ratiometric response to H₂S with a minimum detection limit of 30 nM.Besides,relied on the specific interaction between Pd²⁺and H₂S,the probe presented an excellent selective ratiometric response to H₂S relative to other anionic species and thiols.Moreover,the probe was also suitable for the detection of H₂S in different actual complex samples.This H₂S detection strategy has the characteristics,such as low cost,portability,and smooth operation,and is expected to be used in biological analysis.3.We synthesized Pt/Pt?IV?methylene blue coordination polymers nanoshuttles?Pt/PtMBCPsNSs?photosensitizer for drug synthesis and chemo-photodynamic tumor therapy in vivo.The as-prepared Pt/PtMBCPsNSs as sequential catalysts could decompose into small-sized nanoparticles in the tumor microenvironment?TME?and effectively catalyze the endogenous H₂O₂ to O₂.Meanwhile,substantial singlet oxygen?¹O₂?was generated upon laser irradiation.Subsequently,the ¹O₂ could selectively photo-oxidize non-toxic 1,5-dihydroxynaphthalene?DHN?to yield a considerable amount of desired anticancer agent juglone.Both in vitro and in vivo experiments confirmed that highly toxic ¹O₂ and juglone could trigger apoptosis of cancer cells and effectively inhibit tumor growth.Significantly,on-demand drug synthesis of Pt/PtMBCPsNSs in cells greatly enhanced tumor-specific killing and remarkably reduced side effects to healthy tissues.Therefore,this study provides a promising strategy for the synthesis of specific drugs in tumors and effective synergistic therapy.4.A new type of Pt?IV?methylene blue coordination polymers nanoshuttles?PtMBCPsNSs?photosensitizer was synthesized,and it was found that such photosensitizer can sensitize TiO₂ to achieve visible light-driven photocatalytic water reduction to produce H₂.The generation of H₂ can eliminate excess reactive oxygen species in macrophages?RAW264.7?,thereby achieving the purpose of relieving and treating inflammation.In addition,the introduction of PtMBCPsNSs not only broadened the absorption range of TiO₂,but also enhanced the photocatalysis ability of TiO₂ to produce H₂ under visible light.The mechanism of such catalytic reaction is that the electrons of PtMBCPsNSs transfer from the ground state to the excited state,and further transfer to the conduction band position of TiO₂ under laser irradiation,thereby reducing water to H₂.In vitro cell experiments showed that TiO₂/PtMBCPsNSs had little cytotoxicity,and the produced H₂ can diffuse into the cells through the biofilm and reduce excess reactive oxygen species in RAW264.7cells,thus achieving obvious improvement in inflammation.