ChEMS Seminar: Programming Nanomaterials with Biomolecules: Design and Utility in Tissue Targeting

Professor Nathan C. Gianneschi

University of California, San Diego

Bio: Nathan C. Gianneschi received his B.Sc(Hons) at the University of Adelaide in 1999 with a thesis under the auspices of Dr. Louis M. Rendina in organometallic chemistry. In 2005 he completed his Ph.D at Northwestern University with Professor Chad A. Mirkin studying synthetic allosteric catalysts as mimics of enzymes. Following a Dow Chemical postdoctoral fellowship at The Scripps Research Institute with Professor M. Reza Ghadiri, in 2008 he joined the University of California, San Diego, where he is an associate professor of Chemistry & Biochemistry and Materials Science & Engineering. The Gianneschi group takes an interdisciplinary approach to nanomaterials research with a focus on multifunctional materials with interests that include biomedical applications, programmed interactions with biomolecules and cells, and basic research into nanoscale materials design, synthesis and characterization. For this work Professor Gianneschi has been awarded the NIH Director's New Innovator Award, the NIH Director's Transformative Research Award and the White House's highest honor for young scientists and engineers with a Presidential Early Career Award for Scientists and Engineers (PECASE). Professor Gianneschi was awarded a Dreyfus Foundation New Faculty Award, is a Kavli Fellow of the National Academy of Sciences, and is an Alfred P. Sloan Foundation Fellow.

Programming Nanomaterials with Biomolecules:  Design and Utility in Tissue Targeting

The goal of targeted therapeutics and molecular diagnostics is to accumulate drugs or probes at the site of disease in higher quantities relative to other locations in the body. To achieve this, there is tremendous interest in the development of nanomaterials capable of acting as carriers or reservoirs of therapeutics and diagnostics in vivo.^[1] Generally, nanoscale particles are favored for this task as they can be large enough to function as carriers of multiple copies of a given small molecule, can display multiple targeting functionalities, and can be small enough to be safely injected into the blood stream. The general goal is that particles will either target passively via the enhanced permeability and retention (EPR) effect, actively by incorporation of targeting groups, or by a combination of both.^[2] Nanoparticle targeting strategies have largely relied on the use of surface conjugated ligands designed to bind overexpressed cell-membrane receptors associated with a given cell-type.^[3] We envisioned a targeting strategy that would lead to an active accumulation of nanoparticles by virtue of a supramolecular assembly event specific to tumor tissue, occurring in response to a specific signal. The most desirable approach to stimuli-induced targeting would be to utilize an endogenous signal, specific to the diseased tissue itself, capable of actively targeting materials introduced via intravenous (IV) injection. We present the development of nanoparticles capable of assembling in vivo in response to selective, endogenous, biomolecular signals. For this purpose, we utilize enzymes as stimuli, rather than other recognition events, because they are uniquely capable of propagating a signal via catalytic amplification. We will describe their development and utility as a multimodal imaging platform, and discuss their potential as carriers capable of targeting tissue via a new mechanism.

[1]              J. A. Hubbell, A. Chilkoti, Science, 337, 303-305.

[2]              a) Y. Matsumura, H. Maeda, Cancer Res 1986, 46, 6387-6392; b) D. Peer, J. M. Karp, S. Hong, O. C. Farokhzad, R. Margalit, R. Langer, Nat. Nanotechnol. 2007, 2, 751-760.

[3]              a) W. Arap, R. Pasqualini, E. Ruoslllahti, Science 1998, 279, 377-380; b) D. Pan, J. L. Turner, K. L. Wooley, Chem. Commun. 2003, 2400-2401; c) A. R. Hilgenbrink, P. S. Low, J. Pharm. Sci. 2005, 94, 2135-2146.