Gold Nanoparticles Loaded with Cullin-5 DNA Increase Sensitivity to 17-AAG in Cullin-5 Deficient Breast Cancer Cells

Overview

Journal Int J Pharm

Specialties Chemistry
Pharmacology

Date 2019 Apr 19

PMID 30999048

Citations 8

Authors

Sarah Talamantez-Lyburn

Pierce Brown

Nicole Hondrogiannis

Janaysha Ratliff

Sarah L Wicks

Ninna Nana

Zheng Zheng

Zeev Rosenzweig

Ellen Hondrogiannis

Mary Sajini Devadas

Elana S Ehrlich

Affiliations

Soon will be listed here.

Abstract

HSP90 inhibitors have the potential to treat many types of cancer due to the dependence of tumor cells on HSP90 for cell growth and proliferation. The Cullin-5 (Cul5) E3 ubiquitin ligase is required for HSP90 inhibitors to induce client protein degradation and subsequent cell death. Cul5 is expressed at low levels in breast cancer cells compared to patient matched controls. This observed low Cul5 expression may play a role in the reported decreased efficacy of 17-AAG and related HSP90 inhibitors as a monotherapy. We have developed a method for delivery of 17-AAG plus Cul5 DNA to cells via gold nanoparticles (AuNPs). Delivery of AuNPs containing Cul5 DNA increases the sensitivity of Cul5 deficient AU565 cells to 17-AAG. Characterization of AuNPs by UV-vis spectrum, TEM, gel electrophoresis assay and H NMR indicate attachment of both 17-AAG and DNA payload as well as AuNP stability. Studies in Cul5 deficient AU565 cells reveal that delivery of Cul5 and 17-AAG together increase cytotoxicity. Our results provide evidence that delivery of DNA with drug may serve as a method to sensitize drug resistant tumor cells.

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