Chiral Gold Nanomaterials Precise Synthesis For Biomarker Biological Analysis On Aging And Neurodegenerative Diseases

In this paper,we focus on the synthesis,structure regulation,and the biological effects of chiral nanomaterials.CPL-induced synthesis of chiral gold nanoparticles achieves the elimination of senescent microglia.Besides,a near-infrared light（NIR）-responsive chiral tetrahedron can selectively accelerate the apoptosis of senescent cells,which showed effective treatment on aging and age-related diseases.In addition,a chiral dual-core satellite nanoassembly has been prepared.The mechanical force was generated under CPL irradiation,which accelerate the differentiation of neural stem cells into neurons and has been used for the treatment of Alzheimer’s disease.Firstly,a photosynthetic method is induced to synthesis chiral gold nanoparticles,using gold nanoprisms as seeds and L-CYP,D-CYP（cysteine and phenylalanine dipeptide）as chiral ligands.594 nm laser at 84 m W/cm² for 30 min irradiation under different polarization conditions were used for chiral L-P⁺NPs,or D-P^-NPs synthesis,with a g value of 0.44.The prepared chiral gold nanoparticles were modified with antibodies（anti-Decoy Receptor 2,anti-Dc R2 and anti-beta-2-Microglobulin,anti-B2MG）to target senescent cells and can selectively remove senescent microglia under 808 nm irradiation.The L-P⁺NPs displayed a better effect than D-P^-NPs.After 2 months of light treatment,theα-synuclein aggregates in the PD mice are reduced,and dopamine neurons increased.Forthermore,the athletic ability return to normal level.Secondly,Au₂₀-Au₃₀ tetrahedron（UAu Te）with UCNP in the center is constructed,which can selectively accelerate the apoptosis of senescent cells.When the anti-B2MG on the Au NPs recognizes senescent cells,NIR induces the decomposition of the UAu Te framework by breaking the borate bond.Subsequently,the Granzyme B exposed on the UCNP induces apoptosis in senescent cells,which could be tracked by the changes of UCNP luminescence（UCL）.Compared with single Granzyme B,the UAu Te can not only control the targeted release of Granzyme B,but also initiate the apoptosis program in the absence of perforin.In addition,animal experiment results show that after 30 days of treatment,NIR-responsive tetrahedrons can restore tissue homeostasis,renal function,athletic ability,and hair density in aging mice models.This work shows a potential application prospects for aging.Thirdly,a dual-core satellite chiral nanoassembly was constructed.After incubated with neural stem cells（NSCs）,the dual-core satellite nanoassembly displayed conformational transformation by the generated Fox3 m RNA during cell differentiation,which causes the reversal of the CD signal.Therefore,the differentiation process could be in situ monitored through the CD signal variation after shape-changing of chiral assembly.Importantly,with the switched CPL irradiation,the NSCs differentiation was efficiently accelerated.70.7%of NSCs can successfully differentiate into neurons after 5 days of culture.By measuring the neurites mean length,calcium imaging and membrane potential,it is confirmed that the differentiated neurons have good biological functionsFourthly,when the dual-core satellite chiral nanoassembly is tangled with cytoskeleton fibers,CPL irradiation could accelerate the differentiation of NSCs into neurons.Through cell experiments and simulation calculations,we prove that the dual-core satellite-like nanoassembly generates a mechanical force of 10 n N under CPL irradiation at a frequency of50 Hz,which acts on the cytoskeleton to cause periodic mechanical deformation,and stimulates the neurons differentiation.When differentiated neurons with optimal irradiation protocol were implanted into the hippocampus of AD mice,the amyloid plaques was reduced by more than70%after 3 monthes.Our findings suggest that CPL can guide cellular development for biomedical use.