Dendrimer-Triglycine-EGF Nanoparticles for Tumor Imaging and Targeted Nucleic Acid and Drug Delivery

Abstract

We designed an epidermal growth factor (EGF)-containing polyamidoamine (PAMAM) Generation 4 dendrimer vector labeled with quantum dots for targeted imaging and nucleic acid delivery. 1H NMR, SDS-PAGE, and Western blotting were applied to characterize the synthesized G4.0-GGG-EGF nanoparticles. Targeting efficiency, cell viability, proliferation, and intracellular signal transduction were evaluated using HN12, NIH3T3, and NIH3T3/EGFR cells. We found that EGF-conjugated dendrimers did not stimulate growth of EGFR-expressing cells at the selected concentration. Consistent with this, minimal stimulation of post-receptor signaling pathways was observed. These nanoparticles can localize within cells that express the EGFR in a receptor-dependent manner, whereas uptake into cells lacking the receptor was low. A well characterized vimentin shRNA (shVIM) and yellow fluorescent protein (YFP) siRNA were used to test the delivery and transfection efficiency of the constructed targeted vector. Significant knockdown of expression was observed, indicating that this vector is useful for introduction of nucleic acids or drugs into cells by a receptor-targeted mechanism.

Department(s)

Chemical and Biochemical Engineering

Comments

Studies described herein were supported in part by the Dentistry-Engineering-Pharmacy Interdisciplinary Research Program at Virginia Commonwealth University through a grant to W.A.Y. and H.Y. and an NIH grant ( R21NS063200 ) to H.Y.

Keywords and Phrases

Dendrimer; EGF; Gene delivery; Gene knockdown; HNSCC; Imaging; Nanoparticles; Quantum dots; RNAi; SiRNA; Vimentin; YFP

International Standard Serial Number (ISSN)

1368-8375

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2010 Elsevier Ltd., All rights reserved.

Publication Date

01 Sep 2010

PubMed ID

20729136

Link to Full Text

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