Imaging of gold dendrimer nanocomposites in cells
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Imaging of gold dendrimer nanocomposites in cells Jonathan D. Eichman✺ , Mohamed K. Khan✞,Inhan Lee✺ , James R. Baker, Jr., ✺ Theodore S. Lawrence✞, Dorothy R. Sorenson✙, Chris A. Edwards✙ and Lajos Balogh✟ ✺ ✺
Center for Biologic Nanotechnology, Department of Cell & Development Biology ✞ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109-0533 ✙
ABSTRACT Dendrimer nanocomposites (DNC) are hybrid nanoparticles formed by the dispersion and immobilization of guest atoms or small clusters in dendrimer matrices. They have a great potential in biomedical applications due to their controlled composition, predetermined size, shape and surface functionalities. In this work, nanocomposites of gold and poly(amidoamine) dendrimers {Au(0)n-PAMAM} have been selected to demonstrate this nanoparticle based concept. {Au(0)n-PAMAM} gold dendrimer nanocomposites with a well-defined size have been synthesized and imaged by TEM both in vitro and in vivo. Dendrimer nanocomposites have also the potential to be used as drug delivery vehicles either utilizing bioactive guests or incorporating radioactive isotopes. Radioactive dendrimer nanocomposites, e.g. {198-Au}, can be delivered to the tumor either by means of injecting the active nanoparticles directly into the tumor microvasculature or by intravenous injection. Both specific or non-specific targeting can be utilized in this process to achieve appropriate transfer. INTRODUCTION Poly(amidoamine) (PAMAM) dendrimers contain beta-alanine repeat units thus can be viewed as spherical artificial proteins that may be used as nanoscopic building blocks. However, PAMAM dendrimers are aliphatic, therefore they are extremely difficult to observe directly in cells or in tissue. Generally, attachment of fluorescent markers, radioactive substituents or surface complexes of metal ions, such as Gd3+ are used to overcome this obstacle. Nonetheless, conjugation of markers to the surface of the macromolecule may dramatically change the solubility and other surface-related properties. This problem can readily be solved by using dendrimer nanocomposites (DNC) that can contain different guests. These nearly monodisperse nanoparticles may readily be created and using DNCs commonly inorganic particles or insoluble drugs can be manipulated as if they were an organic polymers. Dendrimer nanocomposites can be synthesized with various surface properties and are easy to observe by transmission electron microscopy. They readily penetrate into cells and their interaction with biological objects may be adjusted by modifying the properties of the template dendrimers. Dendrimers. Dendrimers are monodisperse symmetric macromolecules containing connectors and branching units built around a small molecule or a linear polymer core1-4. ✟
Corresponding author: The University of Michigan Center for Biologic Nanotechnology, 4010 Kresge Research Building II, 200 Zina Pitcher Place, Ann Arbor, MI 48109-0533. Phone: (734) 615-0623, Fax: (734) 615-0621, [email protected]
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