Monitoring the Biodegradation of Dendritic Near-Infrared Nanoprobes by in Vivo Fluorescence Imaging

Adah Almutairi†, Walter J. Akers‡, Mikhail Y. Berezin‡, Samuel Achilefu*‡ and Jean M. J. Frchet*†
College of Chemistry, University of California, Berkeley, California 94720-1460, and Department of Radiology, School of Medicine, Washington University, St. Louis, Missouri 63110
Mol. Pharmaceutics, 2008, 5 (6), pp 1103–1110
DOI: 10.1021/mp8000952
Publication Date (Web): October 20, 2008
Copyright © 2008 American Chemical Society
* To whom correspondence may be addressed. J.M.J.F.: College of Chemistry, University of California, 718 Latimer Hall, Berkeley, CA 94720-1460; tel, (510) 643-3077; fax, (510) 643-3079; e-mail, frechet@berkeley.edu. S.A.: Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110; tel, (314) 362-8599; e-mail, achilefus@mir.wustl.edu., †

University of California.

, ‡

Washington University.

Abstract

Abstract Image

Synthetic polymers and dendrimers have been widely used by the medical community to overcome biological barriers and enhance in vivo biomedical applications. Despite the widespread use of biomaterials it has been generally extremely difficult to monitor noninvasively their fate in vivo. Here we report multilayered nanoprobes, consisting of a near-infrared core, nanoencapsulated in a biodegradable dendrimer, and surrounded by a shell of polyethylene oxide. Covalent encapsulation of the near-infrared fluorophores in the dendritic scaffold conferred enhanced stability to the nanoprobe with added resistance to enzymatic oxidation and prolonged blood residence time. Insight into the time course of biodegradation of the dendritic aliphatic polyester nanoprobe was gained using noninvasive whole body in vivo fluorescence lifetime imaging. As the dendritic shell biodegrades the NIR probe becomes exposed, enabling monitoring of fluorescence lifetime changes in vivo.

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History

  • Published In Issue December 01, 2008
  • Article ASAPOctober 21, 2008
  • Received: July 18, 2008
    Accepted: September 23, 2008
    Revised: September 18, 2008

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