Bioengineering Seminar Series: Gang Zheng

Wednesday, May 7, 2008
2:00 p.m.-3:00 p.m.
0408 Animal Science/Agriculture Engineering Bldg.
Professor Yu Chen
(301) 405-3439
yuchen@umd.edu

Molecular Beacons and Nano-Beacons for Cancer Imaging and Therapy

Presented by Gang Zheng
Associate Professor of Medical Biophysics, University of Toronto
Associate Professor, IBBME (cross appointment), University of Toronto
Associate Professor of Radiology (adjunct), University of Pennsylvania

Molecular beacons are target-activatable probes that use the fluorescent resonance energy transfer principle to control their fluorescence emission in response to specific biological stimuli. They are useful tools for cancer imaging because of their potential for improving imaging specificity (activation through tumor-specific enzymes or mRNAs) and sensitivity (signal amplification from non-fluorescent to highly fluorescent) as well as their ability to interrogate a wide range of molecular abnormalities. We have introduced the first therapeutic beacons, called “photodynamic molecular beacons (PMB)”. The PMB comprises a disease-specific linker (e.g., peptides or oligonucleotides), a photosensitizer and a quencher. This configuration allows the photosensitizer’s phototoxicity to be silenced until the specific linker-target interactions (e.g., protease-mediated linker cleavage). Thus, the beacons can achieve a very high level of PDT treatment selectivity by destroying only the targeted cancer cells, while leaving non-targeted (normal) cells unharmed.

Nano-Beacons are lipoprotein-like multifunctional nanoprobes based on chemically modified lipoproteins or artificially engineered lipoprotein-mimetic nanoscaffolds. Through a network of amphipathic α-helix-lipid interactions these biocompatible nano-beacons offer exquisite size control at the ideal size range (large enough to avoid renal clearance and small enough to mitigate reticuloendothelial system uptake) thus improving particle circulation kinetics and delivery efficiency. We have introduced several simple and versatile targeting strategies to deliver these lipoprotein-like nanoparticles to any receptor of choice (e.g., epidermal growth factor receptor) thus overcoming the narrow purview of lipoprotein receptor-relevant diseases. Therefore, we can tailor these nano-beacons in terms of their functional payloads (imaging—MRI and optical probes; therapy—PDT agents, drugs and siRNAs) and targeting ligands (e.g., peptides and aptamers, etc.) for personalized treatment and diagnosis of cancer and other diseases.

Audience: Graduate  Faculty 

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