Targeted inactivation of EPS8 using dendrimer-mediated delivery of RNA interference

Quan Yuan; William Andrew Yeudall; Eunmee Lee; Hu Yang

doi:10.1016/j.ijpharm.2018.12.060

Targeted inactivation of EPS8 using dendrimer-mediated delivery of RNA interference

Quan Yuan, William Andrew Yeudall, Eunmee Lee, Hu Yang

Oral Biology & Dx Sciences

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Pages (from-to)	178-181
Number of pages	4
Journal	International Journal of Pharmaceutics
Volume	557
DOIs	https://doi.org/10.1016/j.ijpharm.2018.12.060
State	Published - Feb 25 2019

Keywords

Dendrimer
EGFR
Oral cancer
Signal transduction
Targeted therapy

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.ijpharm.2018.12.060

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title = "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.",

keywords = "Dendrimer, EGFR, Oral cancer, Signal transduction, Targeted therapy",

author = "Quan Yuan and Yeudall, {William Andrew} and Eunmee Lee and Hu Yang",

note = "Funding Information: This work was supported, in part, by the National Science Foundation (CAREER award CBET0954957 ). Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

year = "2019",

month = feb,

day = "25",

doi = "10.1016/j.ijpharm.2018.12.060",

language = "English (US)",

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pages = "178--181",

journal = "International Journal of Pharmaceutics",

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AU - Yuan, Quan

AU - Yeudall, William Andrew

AU - Lee, Eunmee

AU - Yang, Hu

PY - 2019/2/25

Y1 - 2019/2/25

N2 - 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.

AB - 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.

KW - Dendrimer

KW - EGFR

KW - Oral cancer

KW - Signal transduction

KW - Targeted therapy

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JO - International Journal of Pharmaceutics

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Targeted inactivation of EPS8 using dendrimer-mediated delivery of RNA interference

Abstract

Keywords

ASJC Scopus subject areas

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