Gold nanoparticles, nanomedicine, cancer therapy

The impact of nanotechnology is colossal. Nanotechnology has enormous job-growth prospects due to its wide range of applications. According to a recent study conducted by the market research agent, Global Information Inc., the annual market for products applying nanotechnology will exceed US $3 trillion worldwide by 2018. In medical applications, Gold nanoparticles (GNP) are promising as agents for cancer or photothermal therapies, carriers for drug delivery, and contrast agents for biological imaging and sensing [1-3]. They are in many ways (higher photostability, lower toxicity, stronger two-photon luminescence, tunable absorption band, ability to bind bio-molecules, etc.) superior to organic fluorescent molecules, making them excellent fluorescence probes for biological imaging. 

In this project, the researcher will use the latest fluorescence lifetime imaging (FLIM)-FRET (Förster resonance energy transfer, so called ‘nanometer spectroscopic ruler'; FLIM-FRET techniques have been used to assess drug efficacy in cancer therapies [4, 5], diagnosis of diseases [6, 7], understanding brain functions [8], or drug developments [9, 10]) to understand the mechanism of the entry of GNPs into various cancer cells. Instead of using complicated time-domain analysis tools, we will use an innovative phasor analysis tool [11] to study the FRET and therefore the endocytosis of GNPs in cells. We will also investigate the applications of GNPs for nucleic acid sensing. The study would potentially open up new possibilities in cancer diagnosis and therapies. The research outcomes will be also valuable for physicists to evolve the synthesis for high-yield GNPs. 

1.       S. Jain, D. G. Hirst, and J. M. O'sullivan, "Gold nanoparticles as novel agents for cancer therapy," Br. J. Radiol. 85, 101-113, 2012.

2.       G. Wei et al., "Revealing the photophysics of gold-nanobeacons via time-resolved fluorescence spectroscopy," Opt. Lett. 40, Nov. 2015.

3.       D. Li, H. Yu, and Y. Chen, "Fast bi-exponential fluorescence lifetime imaging analysis methods," Opt. Lett. 40, 336-339, 2015.

4.       L. Shang, N. Azadfar, F. Stockmar, W. Send, V. Trouillet, M. Bruns, D. Gerthsen, and G. U. Nienhaous, "One-pot synthesis of near-infrared fluorescent gold clusters for cellular fluorescence lifetime imaging," Small 7(18), 2614-2620, 2011.

1. R. Weissleder and M. Pittet, "Imaging in the era of molecular oncology," Nature, 580-89, 2008.

6.       K. Okabe, et al., 'Intracellular temperature mapping with a fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy', Nature Communications 3, 705-708, 2012.

1. G.O. Fruhwirth, et al., 'How FRET imaging improves the understanding of protein interaction networks in cancer biology', ChemPhysChem 12, 442-461, 2011.
2. S. Coda, A. J. Thompson, G. T. Kennedy, K. L. Roche, L. Ayaru, D. S. Bansi, G. W. Stamp, A. V. Thillainayagam, P. M. W. French, and C. Dunsby, "Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe," Biomed. Opt. Express 5(2), 515-538, 2014.
3. E. K. Esbjörner, F. Chan, E. Rees, M. Erdelyi, L. M. Luheshi, C. W. Bertoncini, C. F. Kaminski, C. M. Dobson, and G. S. Kaminski Schierle, "Direct observations of Amyloid self-assembly in live cells provide insights into differences in the kinetics of A(1-40) and A(1-42) aggregation," Chem. Biol. 21(6), 732-742, 2014.
4. A. Esposito, C.P. Dohm, M. Bähr, and F. S. Wouters, "Unsupervised fluorescence lifetime imaging microscopy for high content and high throughput screening," Mol. Cell Proteomics 6(8), 1446-54, 2007.
5. Digman, Michelle A., et al. "The phasor approach to fluorescence lifetime imaging analysis." Biophysical journal 94.2 (2008): L14-L16.