Thursday, February 22, 2007
MECHANISMS OF TRANSPORT ACROSS THE ALVEOLAR EPITHELIAL BARRIER: FROM IONS TO NANOPARTICLES
Edward D. Crandall, Ph.D., M.D.
Will Rogers Institute Pulmonary Research Center
Departments of Medicine and Pathology
Keck School of Medicine
Mork Family Department of Chemical Engineering and Materials Science
Viterbi School of Engineering
University of Southern California
Abstract

Interest in nanotechnology has greatly expanded in recent years, driven in part by growth in manufacturing and applications that range widely from fabrication of useful nanoscale circuitry and robotics to biological applications of nanomaterials in imaging and transduction at the cellular and molecular levels. Nanoparticles promise to be useful for many biomedicine-related applications, yet their toxicity, trafficking characteristics across cells, and specific pathways and mechanisms of uptake into pneumocytes are not well known.

The lung can serve as a portal for entry for nanomaterials (ambient and/or manufactured) into the systemic circulation. Inhaled nanoparticles can be found in heart, bone marrow, blood vessels and other organs, and their most likely route of entry into the circulation is across the epithelia of the lung, especially the alveolar epithelium with its very large surface area and thin barrier thickness. Further knowledge about the mechanisms by which particles injure, interact with and/or are transported across the alveolar epithelium is thus of considerable importance for understanding health effects related to inhalation of nanoparticles in ambient air. Nevertheless, nanoparticle-based drug/gene delivery and other biological applications may be important to pursue, even though biocompatibility and toxicity of such nanomaterials are not yet well defined.

To explore interactions with the air-blood barrier of distal lung, nanoparticle injury of, uptake into and trafficking across alveolar epithelial cells were investigated. Polystyrene nanoparticles (PNP) of different surface charge and size were utilized as models of defined manufactured nanomaterials. Results indicate that (1) all PNP are non-toxic to the cells, (2) PNP translocate transcellularly across rat alveolar epithelial cell monolayers, and (3) transepithelial trafficking of PNP is markedly influenced by nanoparticle surface charge density and size. Specific mechanisms underlying these interactions remain to be fully determined
URL:
http://www.usc.edu/schools/medicine/util/directories/faculty/profile.php?PersonIs_ID=232
Thursday, February 22, 2007
Seminar at 12:45 p.m.
OHE 122
Refreshments served after the seminar in HED Lobby
The Scientific Community is cordially invited.