State Key Laboratory of Medicinal Chemical Biology, College of Chemistry,
Tianjin Key Laboratory of Biosensing and Molecular Recognition,
Tianjin, 300071, China
In Xiao Lab we are applying and developing optical microscopic methods to explore problems in analytical chemistry, biomedicine and nanoscience. One of our main focus areas is the understanding of those ambiguous vital biological processes with functionalized nanomaterials in living cell with high spatial and temporal resolution. Meanwhile, we also have interest in the exploration of the fundamental photophysical properties of novel functional nanomaterials and their potential applications in analytical chemistry for ultrasensitive detection. As our main tool, we are currently adopting single molecule/nanoparticle imaging and spectroscopy techniques to study the cellular uptake mechanisms of drug delivery nanocargos and their fate inside living cells, the substrate induced photophysical variation of organic molecules and the nonlinear optical response of novel functional nanomaterials.
The ultimate limit to analytical sensitivity is the reliable detection of single molecules. Recent technical advances in optical detection and manipulation have made the detection of isolated, light emitting probe molecules a reality. Thus we are witnessing a burgeoning interest in the imaging and spectroscopy of single molecules (or nanoparticles), particularly within the fields of cell biology and drug discovery. Of particular importance to biology is the possibility of direct, real-time visualization of single biological macromolecules and their assemblies under native physiological conditions, offering great promise for enhancing our understanding of the behavior, interactions, mechanisms and trafficking of individual biological macromolecules within the living cell. Such studies have increased medical and pharmaceutical significance within the developing post-genomic era of proteomics, providing the means to track the behavior, kinetics and mechanistic involvement of biochemically relevant single proteins, such as enzymes. More detailedly, our research interest including the following three parts:
Single molecule studies are uniquely poised to yield information about molecular motion, behavior, and fluctuations over time and space. There are many biological molecules that can avail from examination at this level, typical subjects being key members of a system that are receptive to specific cellular signals, environmental perturbations or drug intervention. Cellular mechanisms that have been examined include ion channel activity, protein folding, enzyme activity, membrane structure, molecular motors/motility and vesicle transport. Single molecule detection is a way to study detailed physical and chemical properties that allows for scrutiny of fundamental principles and mechanisms, and may lead to technological and methodological developments. Single molecule techniques also have key potential in material development. The single molecule is an excellent probe of local (nanoscale) properties since it is a quantum light source with spectrum and lifetime that is sensitive to its chemical and physical environment.
A localized surface plasmon (LSP) is the result of the confinement of a surface plasmon in a nanoparticle of size comparable to or smaller than the wavelength of light used to excite the plasmon. The LSP has two important effects: electric fields near the particle’s surface are greatly enhanced and the particle’s optical absorption has a maximum at the plasmon resonant frequency. The enhancement falls off quickly with distance from the surface and, for noble metal nanoparticles, the resonance occurs at visible wavelengths. The plasmon resonant frequency is highly sensitive to the refractive index of the environment; a change in refractive index results in a shift in the resonant frequency. As the resonant frequency is easy to measure, this allows LSP nanoparticles to be used for nanoscale sensing applications. Nanostructures exhibiting LSP resonances are used to enhance signals in modern analytical techniques based on spectroscopy. In our group, we are applying single nanoparticle as the probe for the detection of biomolecules in solution or within living cells with single particle spectroscopy. In addition, we are also developing some robust optical imaging methods for the dynamic tracking of individual plasmonic particles on the cell membrane or inside living cells.
The rotational and translational motion of single nanoparticles can be measured and used to understand the local mechanical properties of the material in which the molecules are embedded. Thus our group is seeking to understand and catalog the great variety of behaviors of single nanoparticles in technologically relevant environments to better use these probes to study the small-scale structure.
19. Liu, H.; Geng, X.; Wang, X.; Wei, L.; Li, Z.; Lin, S.; Xiao, L.*, A Carbonized Fluorescent Nucleolus Probe Discloses RNA Reduction in the Process of Mitophagy. CCS Chemistry 2021, DOI: 10.31635/ccschem.021.202101371. https://www.chinesechemsoc.org/doi/10.31635/ccschem.021.202101371
18. Gen, W.-C.; Ye, Z.; Zheng, Z.; Gao, J.; Li, J.-J.; Shah, M. R.; Xiao, L.*; Guo, D.-S.* Supramolecular Bioimaging through Signal Amplification by Combining Indicator Displacement Assay with Förster Resonance Energy Transfer. Angew. Chem. Int. Ed. 2021, DOI: 10.1002/anie.202104358. https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202104358
17. Wang, X.; Ye, Z.; Hua, J.; Wei, L.; Lin, S.; Xiao, L.*, Fast Surface Restructuring within the Gap of Au Nanocube Dimer for the Enhancement of Catalytic Efficiency. CCS Chemistry 2021, 3, 1185-1197. https://www.chinesechemsoc.org/doi/10.31635/ccschem.021.202100770
16. Ye, Z.; Geng, X.; Wei, L.; Li, Z.; Lin, S.; Xiao, L.*, Length Dependent Distinct Cytotoxic Effect of Amyloid Fibrils beyond Optical Diffraction Limit Revealed by Nanoscopic Imaging. ACS Nano 2021, 15, 934-943. https://pubs.acs.org/doi/abs/10.1021/acsnano.0c07555
15. Xu, J.; Wang, J.; Qiu, J.*; Liu, H.; Wang, Y.; Cui, Y.; Humphry, R.; Wang, N.; Durkan, C.; Chen, Y.; Lu, Y.; Ma, Q.; Wu, W.; Luo, Y.; Xiao, L.*; Wang, G.*, Nanoparticles Retard Immune Cells Recruitment in vivo by Inhibiting Chemokine Expression. Biomaterials 2021, 265, 120392. https://www.sciencedirect.com/science/article/pii/S0142961220306384
14. Yan, Z.; Wang, D.; Ye, Z.; Fan, T.; Wu, G.; Deng, L.; Yang, L.; Li, B.; Liu, J.; Ma, T.; Dong, C.; Li, Z.; Xiao, L.*; Wang, Y.*; Wang, W.*; Hou, J.*, Artificial Aquaporin That Restores Wound Healing of Impaired Cells. J. Am. Chem. Soc. 2020, 142, 15638–15643. https://pubs.acs.org/doi/10.1021/jacs.0c00601
13. Ma, Y.; Ye, Z.; Zhang, C.; Wang, X.; Li, H.; Wang, M. S.; Luo, H.*; Xiao, L.*, Deep Red Blinking Fluorophore for Nanoscopic Imaging and Inhibition of β-Amyloid Peptide Fibrillation. ACS Nano 2020, 14, 11341–11351. https://pubs.acs.org/doi/10.1021/acsnano.0c03400
12. Ye, Z.; Wei, L.; Geng, X.; Wang, X.; Li, Z.; Xiao, L.*, Mitochondrion-Specific Blinking Fluorescent Bioprobe for Nanoscopic Monitoring of Mitophagy. ACS Nano 2019, 13, 11593-11602. https://pubs.acs.org/doi/10.1021/acsnano.9b05354
11. Ling, Y.; Zhang, D.; Cui, X.; Wei, M.; Zhang, T.; Wang, J.; Xiao, L.*; Xia, Y.*, Direct Monitoring Cell Membrane Vesiculation with 2D AuNP@MnO2 Nanosheet Supraparticles at Single-Particle Level. Angew. Chem. Int. Ed. 2019, 131, 10652-10656. https://onlinelibrary.wiley.com/doi/abs/10.1002/ange.201902987
10. Ye, Z.; Wei, L.; Xiao, L.*; Wang, J., Laser Illumination-Induced Dramatic Catalytic Activity Change on Au Nanospheres. Chem. Sci. 2019, 10, 5793-5800. https://pubs.rsc.org/en/content/articlelanding/2019/sc/c9sc01666j#!divAbstract
9. Ye, Z.; Liu, H.; Wang, F.; Wang, X.; Wei, L.; Xiao, L.*, Single-Particle Tracking Discloses Binding-Mediated Rocking Diffusion of Rod-Shaped Biological Particles on Lipid Membranes. Chem. Sci. 2019, 10, 1351-1359. https://pubs.rsc.org/en/content/articlelanding/2019/SC/C8SC04033H#!divAbstract
8. Ye, Z.; Wang, X.; Xiao, L.*, Single-Particle Tracking with Scattering-Based Optical Microscopy. Anal. Chem. 2019, 91, 15327–15334. https://pubs.acs.org/doi/abs/10.1021/acs.analchem.9b02760
7. Zhang, D.; Wei, L.; Zhong, M.; Xiao, L.*; Li, H.-W.; Wang, J., The Morphology and Surface Charge-Dependent Cellular Uptake Efficiency of Upconversion Nanostructures Revealed by Single-Particle Optical Microscopy. Chem. Sci. 2018, 9, 5260-5269. https://pubs.rsc.org/en/content/articlelanding/2018/SC/C8SC01828F#!divAbstract
6. Tan, H.; Huang, Y.; Xu, J.; Chen, B.; Zhang, P.; Ye, Z.; Liang, S.; Xiao, L.*; Liu, Z.*, Spider Toxin Peptide Lycosin-I Functionalized Gold Nanoparticles for in vivo Tumor Targeting and Therapy. Theranostics 2017, 7, 3168-3178. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566113/
5. Xiao, L.*; Yeung, E. S.*, Optical Imaging of Individual Plasmonic Nanoparticles in Biological Samples. Ann. Rev. Anal. Chem. 2014, 7, 89-111. https://www.annualreviews.org/doi/full/10.1146/annurev-anchem-071213-020125
4. Xiao, L.; Wei, L.; Liu, C.; He, Y.; Yeung, E. S.*, Unsynchronized Translational and Rotational Diffusion of Nanocargo on a Living Cell Membrane. Angew. Chem. Int. Ed. 2012, 51, 4181-4184. https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201108647
3. Xiao, L.; Ha, J. W.; Wei, L.; Wang, G.; Fang, N.*, Determining the Full Three-Dimensional Orientation of Single Anisotropic Nanoparticles by Differential Interference Contrast Microscopy. Angew. Chem. Int. Ed. 2012, 51, 7734-7738. https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201202340
2. Xiao, L.; Qiao, Y.; He, Y.*; Yeung, E. S., Imaging Translational and Rotational Diffusion of Single Anisotropic Nanoparticles with Planar Illumination Microscopy. J. Am. Chem. Soc. 2011, 133, 10638-10645. https://pubs.acs.org/doi/abs/10.1021/ja203289m
1. Xiao, L.; Zhao, D.; Chan, W.-H.; Choi, M. M. F.; Li, H.-W.*, Inhibition of Beta 1-40 Amyloid Fibrillation with N-acetyl-L-cysteine Capped Quantum Dots. Biomaterials 2010, 31, 91-98. https://www.sciencedirect.com/science/article/pii/S0142961209009302