(5cd) Probing Living Systems by Nanoparticles

Nanotechnology is revolutionizing the ways how physicians prevent, diagnose and treat diseases. The sizes of nanomaterials are close to those of biomolecules, making it possible to probe or intervene in the processes occurring in living systems at molecular level using the numerous special optical, mechanical, electrical, magnetic and thermal properties of nanomaterials. We synthesized nanoparticles of semiconductors, iron oxides, polymers and lipids, and assembled novel nanocomposites based on the combinations of the individual types of nanoparticles. We used semiconductor nanocrystals (quantum dots) to image and track the intracellular transport of Tat peptide, the peptide sequence used by HIV virus to infect cells, with a focus on the downstream events after the Tat-quantum dot conjugates were internalized by the cells. We developed a technique to deliver and image single quantum dots in living cell cytoplasm. Using this technique, we were able to track the motion of single dynein motor proteins in living cells, generating new insights into how the transport system of living cells works.

Further, we combined quantum dot-mediated fluorescent imaging with magnetic force for probing single molecule biophysics. We incorporated quantum dots and iron oxide nanoparticles into nanocontainers of sizes 10-100 nm, forming fluorescent-magnetic nanocomposites. Biomolecules (e.g. peptides, proteins and DNAs) were conjugated with the nanocomposites. Single bioconjugated nanoparticles (nanocomposites) were then, for the first time, simultaneously manipulated and imaged with magnetic tweezers attached to a fluorescent microscope.

On the other hand, we explored the applications of nanocomposites in clinical imaging, diagnostics and therapeutics. Fluorescent-magnetic nanocomposites (combining quantum dots and iron oxide nanoparticles) were used for combined MRI and fluorescent cancer imaging. MRI can reveal the location of tumors in deep tissues, while fluorescent imaging can offer convenience in visualizing the tumors during surgery. Fluorescent-magnetic nanocomposites were also used to detect circulating tumor cells and T-cells. Therapeutic drugs and SiRNAs were further incorporated into these multifunctional nanoparticles using polymeric nanocontainers. In addition, polymer-based and lipid-based systems were combined to form novel nanocomposites for improved therapeutic effects.

My (the presenting author's) independent research program will have the following themes: (1) developing nanomaterial-based platform technologies for clinical medicine, and (2) seeking fundamental biomedical discoveries using nanotechnologies. Furthermore, I have strong interests in teaching. I have delivered several guest lectures in both undergraduate and graduate courses, with positive feedback. I have also mentored undergraduate students' research, successfully leading to publications.