Preparation Of Optically Active Nanoprobes And The Biomarker Analysis Of Diseases

Optically active nanomaterials have attracted widespread interest from researchers due to their different morphologies and composition,endowing them with different properties.This paper is based on the synthesis of optically active nanomaterials,and has prepared plasma gold nanofunctional probes and chiral iron selenide nanoprobes.By precisely adjusting the structure,size,and optical response of the probes,they are applied to disease process regulation and ultra sensitive examinations.Firstly,a plasma core-shell spiky nanorod（CSNRs）with average length and diameter of118.3±3.2 nm and 55.1±2.4 nm（aspect ratio of about 2:1）,respectively,were prepared,exhibiting strong characteristic absorption peaks near 800 nm.The CSNRs was surface-modified with an anti-beta-2-microglobulin（a B2MG）antibody for targeting senescent cell,and the surface modification of triphenylphosphine（TPP）promotes its accumulation in mitochondria.When the modified CSNRs was irradiated with low-power 808 nm NIR light,the strong plasmonic coupling of the core-shell structure and the spiky surface structure effectively activated ROS production,inducing mitochondrial membrane rupture in senescent cells and promoting cell apoptosis.Targeted clearance of senescent cells was achieved in aging model mice by caudal vein injectionin of modified CSNRs.Secondly,ultrasmall chiral gold nanoparticles（D-or L-NPs）modified by D-or L-glutathione ligands were fabricated,with a size of 2.8±0.4 nm.After conjugated with anti-NLRP3 antibodies（D-NP-a NLRP3 or L-NP-a NLRP3）,it effectively targeted the NLRP3protein in microglia,and degraded endogenous NLRP3 protein through TRIM21 dependent proteasome.In addition,the binding of Aβ42 monomer with D-NP was more effective in inhibiting Aβ42 fibrillation,compared with L-NP.Further research has found that D-NP recognized the highly expressed transporter protein SLC3A2 in the blood-brain barrier（BBB）,and the affinity of D-NP to SLC3A2(1.38×10⁷ M^-1)was sixteen-fold higher than that of L-NP.Therefore,D-NP-a NLRP3 could penetrate BBB through SLC3A2,and then enterd microglia to degrade NLRP3 protein.We also found that Aβfibrils induced microglia inflammatory senescence through activating NLRP3 inflammasome.Targeted degradation of NLRP3 can prevented Aβ-mediated microglia senescence,and ameliorate Alzheimer’s disease pathologies and spatial memory.Thirdly,chiral iron selenide nanostructures（L-or D-Fe_xSe_y）with unique morphology were synthesized by one-step method,which can enantiously recognize and bind the SLC7A11 and Tfr1 receptor highly expressed on the surface of tumor cells,and degrade in the tumor microenvironment,showing dose dependent GSH depletion,Fe²⁺release and selenium metabolism.Chiral Fe_xSe_y can induce ferroptosis in tumor cells at extremely low concentrations,triggering ICD,promoting DC maturation,and initiating adaptive CD8 T cell responses.At the same time,chiral Fe_xSe_y also can upregulate the expression of tumor surface receptor proteins NKG2DL（Rae1 and H60b）,activate the NKG2DL/NKG2D pathway,and enhance NK cell recognition and cytotoxicity towards tumour cells.In vivo,more CD8 T and NK cell enrichment and activation were detected in the tumor tissue of B16F10 melanoma model mice injected with L-Fex Sey,which was approximately twice that of D-or DL-Fe_xSe_y mice.After long-term treatment by L-Fe_xSe_y,the tumor tissue was eliminated completely,and a strong immunological memory effect was produced.Fourthly,a new ultrasensitive electrochemical immunosensor for endocrine disruptor nonylphenol was developed using ultrasmall chiral gold nanoclusters（AuNCs）and reduced graphite oxide（rGO）as the assembly substrate,with the detection limit as low as 5.25 ng/L.The sensor was applied to detect the leaching level of nonylphenol in instant noodle barrels/bowls.We collected 61 samples both domestically and internationally,and the detection rate of nonylphenol was approximately 66%.Among them,polyethylene and polystyrene instant noodle barrels/bowls release more nonylphenol than polypropylene instant noodle barrels/bowls.In addition,it was demonstrated in MCF-7 cells that the increased release of nonylphenol was associated with higher estrogen activity in living cells,revealing its potential biological effects.