Journal of Bioequivalence & Bioavailability

Novel approach for the targeting of acidic tissue: pHLIP ? pH (Low) Insertion Peptide

2^nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit-2011 and International Conference on Pharmaceutics & Novel Drug Delivery Systems

06-08 June 2011, Las Vegas, USA

Oleg A. Andreev, Donald M. Engelman and Yana K. Reshetnyak

Scientific Tracks Abstracts: JBB

Abstract:

W e found a way to target acidic tissue in vivo. Our technology is based on the discovery of a pH (Low) Insertion Peptide (pHLIP TM ). pHLIP TM is a 35 residues water-soluble membrane peptide that inserts and folds across lipid bilayer in cells or liposomes in response to low pH. Membrane-associated folding of pHLIP TM occurs within seconds and is accompanied by a release of energy (about 2 kcal/mol) that can be used to target acidic tissue in vivo and move cell-impermeable cargo-molecules across cellular membranes. pHLIP possesses dual delivery capabilities: it can inject and release cargo molecules into the cytoplasm and/or it can tether cargo molecules to the cell surface. In the fi rst scenario, a cargo molecule is attached to the pHLIP C-terminus via a cleavable S-S bond while in the second it is conjugated to the N-terminus via a non-cleavable bond. Among molecules tethered for the surface of cancer cells in vivo are fl uorescent dyes, PET and SPECT imaging agents. Fluorescent pHLIP TM can target primary tumors with high accuracy, mark tumor borders and stain millimeter-sized tumor spots and metastatic lesions. Th e extent of tumor labeling directly correlates with tumor aggressiveness. Among cell-impermebale molecules translocated across a cell membrane are cyclic peptides, toxin ? phalloidin and PNAs. Our technology opens the new opportunity to target cancer tumors with high selectivity and decreased side eff ects

Biography :

Yana K. Reshetnyak is an Associate Professor at the University of Rhode Island and one of the main inventors of pHLIP-technology together with Profs Andreev and Engelman. She has MS in Molecular Physics from the Saint-Petersburg State University, and Ph.D. in Biophysics in Pushchino, Russian Academy of Science, followed by postdoctoral work in the Cancer Center in Texas, and in Yale. In 2003 a National Science Foundation Award took her to the University of Rhode Island. She is a Laureate of the G. Weber International Competition in Biological Fluorescence. He has published more than 40 papers in reputed journals.