UCLA

The common theme of my 5-year PhD research is to channel progress in spin physics and nano-bio-materials into meaningful improvements in the theoretical studies, methodological developments, and advanced applications of magnetic resonance (MR) to:

1) MR Molecular Imaging: to detect lesions (especially cancers) at early stages through imaging the existence and locations of physiologically important biomarkers; and

2) MR Nano Medicine: to cure diseases (especially cancers) by targeted therapy through nanodrugs and hyperthermia.

The research activities had encompassed a balanced approach to develop a rigorous theoretical understanding on sensitively imaging magnetic nanoparticles by active- feedback spin dynamics of selective self-excitation and fixed-point dynamics on one hand and sound methodology with biomedical applicability to early pancreatic cancers and brain tumors detection on the other. Computer simulations, phantom experiments of superparamagnetic nanoparticles, and in vivo experiments of orthotopic pancreatic cancer and brain tumor mouse models had been used to validate the applicability and efficacy of our proposed methods.

The major research projects and achievements with my coworkers under the supervision of Prof. Yung-Ya Lin include:

1) Developed original MR method, "Active-Feedback Fixed-Point Imaging", for early cancer detection, with both quantum and classical formulation of the spin dynamics.

2) Demonstrated 3-5 times of enhancement in the contrast-to-noise ratio (CNR) of early pancreatic cancers which were targeted and labeled by CA19-9 conjugated magnetic nanoparticles by our "Spin Avalanche Amplification" method, based on statistics from 7 orthotopic pancreatic cancer mouse models.

3) Demonstrated 4-10 times of enhancement in the CNR of early GBM (glioblastoma multiforme, the most common and aggressive form of brain cancers) by our "Active-Feedback Fixed-Point Imaging" method, based on statistics from 20 orthotopic GBM mouse models.

4) Developed novel multifunctional, theranostic, smart nanoparticles, called "UCS-Gd-Dox" for MR imaging and targeted cancer therapy. By conjugating Gd3+ at the stable core of unibody core-shell polymer (UCS) and encapsulating doxorubicin (Dox) at the shell in a pH-sensitive manner, we achieved a selective drug release (75% difference between pH 7.4 and 5.5) and MR imaging (r1 = 0.9 and 14.5 mM-1s-1 at pH 7.4 and 5.5, respectively). The anti-cancer effect is significantly better than free cancer drugs in tumor-bearing mouse models, presumably due to enhanced permeability and retention effect and pH-triggered release.

5) Formulated more accurate theoretical description to magnetic resonance hyperthermia, including aggregation/disruption of monomers/clusters and nonlinear response under strong external magnetic field.