Targeted Inactivation of EPS8 using Dendrimer-Mediated Delivery of RNA Interference

Abstract

We developed polyamidoamine dendrimers conjugated with epidermal growth factor (EGF) for use in receptor-mediated delivery of therapeutics to cancer cells. Here, we demonstrate the utility of this approach to inhibit proliferation and migration of head and neck squamous carcinoma cells through targeting of EPS8, a key regulator of squamous carcinoma growth and motility. Use of EGF-dendrimers to deliver siRNA or shRNA against EPS8 resulted in inhibition of cell growth and reduction in cell motility. Moreover, more profound repression of the target protein was obtained with repeat exposure to the targeting reagent, and was consistent with the altered biological properties. Thus, targeting of EPS8 can be achieved with EGF-conjugated dendrimers delivering EPS8-specific RNAi therapeutics, leading to a reduction in the malignant phenotype of cells.

Department(s)

Chemical and Biochemical Engineering

Comments

This work was supported, in part, by the National Science Foundation (CAREER award CBET0954957 ).

Keywords and Phrases

Dendrimer; EGFR; Oral cancer; Signal transduction; Targeted therapy

International Standard Serial Number (ISSN)

0378-5173

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2019 Elsevier B.V., All rights reserved.

Publication Date

25 Feb 2019

PubMed ID

30597261

Link to Full Text

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