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



4) Biomedical Applications of Functional Nanomaterials



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 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, 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. 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



    1. 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。

    2. 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。

    3. 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,实现对催化反应单颗粒水平的实时原位表征,对揭示单个纳米颗粒在催化反应中的异质性和动力学行为有着重要意义。超分辨成像技术主要包括单分子定位显微镜技术(SLM),光激活定位显微镜技术(PALM),随机光学重建显微镜技术和直接光学重建显微镜技术(STORM)。超分辨成像技术打破了光学显微镜的衍射极限,不仅可以在单个纳米颗粒催化反应中对单个产物实现分辨率达到 10 nm的成像,而且实现密集样本下对生物结构、组成和一些动态生物过程的超高精度揭示,因此,超分辨成像技术在纳米催化、生物医学等领域得到了高度的认可和广泛的应用。我们团队致力于利用超分辨成像技术研究单颗粒催化反应,旨在更有效、更直观地揭示单个颗粒表面不同位点催化活性的差异性,使单颗粒催化异质性的研究得到进一步深化。

    4. 功能纳米材料的设计及其生物医学应用