Research Abstract:
Accurate and rapid detection of tumors is of great importance for assessing the molecular basis of cancer pathogenesis, preventing disease complications, and implementing a tailored therapeutic regimen. For these reasons, we design and develop new molecular probes and nanomaterials for imaging the expression of aberrant genes, proteins, and other pathophysiologic processes. To utilize optical methods for cellular and in vivo imaging by optical methods, we focus on developing materials that are fluorescent in the near infrared wavelength region (700-900 nm) of the electromagnetic spectrum where light can penetrate deep in thick tissue. Specific delivery of the contrast agents to target cell organelles or tissue is accomplished by linking the agents to bioactive molecules such as peptides, proteins, and drugs. Alternatively, the inherent chemical properties of the contrast agents provide a mechanism to monitor cell trafficking or physiological processes such as tissue hypoxia and ion transport in cells.
Another aspect of our program research involves the biological evaluation of the new materials to assess ligand trafficking in cells, cytotoxicity, cell proliferation, subcellular distribution, enzyme kinetics, and activation of specific molecular pathways in cells. Cell biology and biochemistry methods are used. The materials are also used to answer biological questions in vivo by developing the appropriate animal models. Small animal molecular imaging of pathologic tissues with state-of-the-art optical imaging systems completes the feasibility studies before human studies.
We are also developing tissue-specific multi-modal imaging molecules that harness the strengths of optical with other imaging methods such as magnetic resonance and radionuclear (positron and single photon emission) imaging systems. Such multimodal imaging approach with multi-functional nanomolecules and nanoparticles will enable the full realization of the potential for noninvasive cellular and molecular imaging of pathologic tissues, including monitoring of drug action in vivo. Finally, we are also developing tumor-specific Type I and II photodynamic therapy drugs that have both diagnostic and therapeutic potential.
Representative instruments available to researchers and students in our lab include a NIR-compatible confocal FV 1000 microscope, planar multimodal optical scanner for small animals, time-domain and frequency-domain diffuse optical imaging systems, UV-vis spectrophotometer, and spectrofluorometer, LC-MS system, and conventional laboratory equipment. We also collaborate extensively with many laboratories. Our projects provide interdisciplinary training to students and postdoctoral fellows.
Selected Publications:
Bloch S, Xu B, Ye Y, Liang K, Nikiforovich GV, Achilefu S. Targeting Beta-3 integrin using a linear hexapeptide labeled with a near-infrared fluorescent molecular probe. Mol Pharm 2006 3:539-549.
Achilefu S, Bloch S, Markiewicz MA, Zhong T, Ye Y, Dorshow RB, Chance B, Liang K. Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression. Proc Natl Acad Sci USA 2005 102:7976-7981.
Bloch S, Lesage F, McIntosh L, Gandjbakhche A, Liang K, Achilefu S. Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice. J Biomed Opt 2005 10:054003.
Patwardhan SV, Bloch SR, Achilefu S, Culver JP. Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice. Optics Express 2005 13:2564-2577.
Ye Y, Bloch S, Achilefu S. Polyvalent carbocyanine molecular beacons for molecular recognitions. J Am Chem Soc 2004 126:7740-7741.
Last Updated: 07/15/2009 |