Welcome to Xiao Lab at Nankai University!

State Key Laboratory of Medicinal Chemical Biology, College of Chemistry,
Tianjin Key Laboratory of Biosensing and Molecular Recognition,
Nankai University,
Tianjin, 300071, China

Research Interest

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:

1) Single-Particle Counting 

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.

2) Single-Particle Tracking 

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.

3)  Single-Particle Reactions

Nanoparticle-based heterogeneous catalysis has attracted considerable attention in many important chemical transformations, including organic synthesis, pollutant removal and energy production. Among those diverse nanostructures, metal nanoparticle is one of the most important heterogeneous catalyst with excellent or even new catalytic properties due to its high surface-to-volume ratio and chemical potentials. However, the spatial−temporal-dependent catalytic information is yet difficult to be disclosed from ex situ results in bulk solution, which only reflects ensemble-averaged properties from heterogeneous samples. Single-molecule imaging has been proved to be a robust tool to elucidate the catalytic reactions in situ from individual particles. By removing ensemble averaging, one can follow the reactions at the single-turnover resolution and elucidate the distributions from statistical analysis. Herein, we are seeking  reveal and understand the heterogeneity and kinetics of catalytic reactions at the single-particle level by using optical microscopic imaging technology.

     主要研究领域:

    本团队主要围绕分子识别、动态示踪和纳米催化超分辨成像等方面开展研究。主要以功能纳米材料或有机分子为探针,利用光学显微成像技术的高灵敏、高通量检测分析能力,发展一系列先进成像技术,并且针对目前化学生物学、分析化 学以及光物理化学中的基础原理和前沿应用进行深入探究。在单分子、单颗粒水平,探讨功能材料的光物理学特性,分子的自组装机理,重大疾病的致病起因等,从而为上述问题的解决提供参考依据。在活细胞层面,我们探讨功能化纳米材料与细胞膜的作用方式和机制,建立高效运输药物的途径,提供定向、可控且方便易行的药物释放方法,从而为重大疾病的早期诊断与治疗提供有效策略。

单颗粒分子识别: 一方面,我们致力于构筑新型功能性纳米材料,包括不同形貌和粒径的贵金属纳米粒子、上转换纳米粒子、聚合物纳米粒子和量子点等无机纳米粒子,并且与多糖、蛋白、酶等生物大分子以及有机荧光分子等结合,构筑新型杂化纳米探针。另一方面,基于对多种光学显微成像技术的深入学习,我们致力于优化和发展单颗粒/单分子光学显微成像技术,不断突破当前在检测条件和检测水平方面的局限性,提高时空分辨率。旨在实现在单分子水平上对重金属离子、生物大分子等的特异性识别和超灵敏检测,为环境治理和重大疾病的早期诊疗提供新途径。

单颗粒动态示踪:单颗粒示踪技术是一种超高灵敏度以及高时空分辨率的显微成像手段,能够对细胞膜、细胞内的一些动力学过程进行长时间的成像追踪。我们致力于构筑适合于单颗粒动态示踪成像的纳米探针,例如贵金属纳米粒子、生物大分子结构、量子点等。一方面,研究细胞膜上的动态行为,包括纳米探针入侵细胞的方式和作用机制,细胞膜上多糖、蛋白等不同生物大分子对于纳米探针的识别、粘附、迁移和扩散行为的重要作用。另一方面,研究细胞内部的动态过程,包括颗粒和分子的内化作用与代谢过程,分子信号的传递与转导,基因调控等。旨在借助单颗粒示踪成像技术揭示某些疾病的发病机制,从而实现对疾病的预防和诊断,并且为构筑新型纳米药物递送材料提供指导。

单颗粒化学反应多相催化在化学反应中扮演着重要的角色包括有机合成、能源反应以及污染物的清除等在近几十年, 得到了研究者的广泛关注金属纳米颗粒具有较小的尺寸和较高的化学势在催化反应中表现出优异的催化性能是一种重要的多相催化剂被广泛地应用于各种催化反应中。传统的催化反应研究主要聚焦于对催化反应整体平均的测量假设多相催化剂和催化反应在时间和空间上是异质性的然而对于任意催化反应中单个催化剂催化活性异质性的实际分析与表征仍然是个巨大的挑战。基于此,课题组利用光学显微成像技术,致力于从单颗粒、单分子反应的角度去进一步揭示和理解催化反应中的异质性及相关动力学。

代表性论文:

22. Chen,M ,Ye, Z, Wei,L ,Yuan, J, Xiao, L.*Shining at the Tips: Anisotropic Deposition of Pt Nanoparticles Boosting Hot Carrier Utilization for Plasmon-Driven Photocatalysis.  J. Am. Chem. Soc.2022, DOI: https://doi.org/10.1021/jacs.2c04202. https://pubs.acs.org/doi/10.1021/jacs.2c04202

21. Ye, Z.;  Yan, Z.-J.; Zhang, C.; Hou, J.-L.*;  Yue, S.*;  Xiao, L.*,  Charged Tubular Supramolecule Boosting Multivalent Interactions for the Drastic Suppression of Aβ Fibrillation. Nano Lett. 2021, 21, 10494–10500. https://doi.org/10.1021/acs.nanolett.1c04007

20. Wang, T.; Wang, X.; Wang, H.; Li, L.; Zhang, C.; Xiang, R.; Tan, X.; Li, Z.; Jiang, C.; Zheng, L.; Xiao, L.*Yue, S.*, High TSPAN8 expression in epithelial cancer cell-derived small extracellular vesicles promote confined diffusion and pronounced. J. Extracell. Vesicles 2021, 10, 12167. https://onlinelibrary.wiley.com/doi/full/10.1002/jev2.12167

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, 3, 3081–3093https://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, 60, 19766 –19771.  https://doi.org/10.1002/anie.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 2021265, 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@MnONanosheet Supraparticles at Single-Particle Level. Angew. Chem. Int. Ed. 2019, 58, 10542-10546.    https://doi.org/10.1002/anie.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. 201910, 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 MicroscopyAnal. 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. 20189, 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. 20147, 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. 201251, 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. 201251, 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. 2011133, 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