Biomaterials, Biodegradables and Biomimetics Research Group

Papers in Scientific Journals

Targeting of EGFR, VEGFR2 and Akt by engineered dual drug encapsulated mesoporous silica-gold nanoclusters sensitizes tamoxifen-resistant breast cancer

Abstract

Tamoxifen administration enhanced overall disease-free survival and diminished mortality rates in cancer patients. However, patients with breast cancer often fail to respond for tamoxifen therapy due to the development of a drug-resistant phenotype. Functional analysis and molecular studies suggest that protein mutation and dysregulation of survival signaling molecules such as epidermal growth factor receptor, vascular endothelial growth factor receptor 2, and Akt contribute to tamoxifen resistance. Various strategies, including combinatorial therapies, show chemosensitize tamoxifen-resistant cancers. Based on chemotoxicity issues, researchers are actively investigating alternative therapeutic strategies. In the current study, we fabricate a mesoporous silica gold cluster nanodrug delivery system that displays exceptional tumor-targeting capability, thus promoting accretion of drug indices at the tumor site. We employ dual drugs, ZD6474, and epigallocatechin gallate (EGCG) that inhibit EGFR2, VEGFR2, and Akt signaling pathways since changes in these signaling pathways confer tamoxifen resistance in MCF 7 and T-47D cells. Mesoporous silica gold cluster nanodrug delivery of ZD6474 and EGCG sensitize tamoxifen-resistant cells to apoptosis. Western and immune-histochemical analyses confirmed the apoptotic inducing properties of the nanoformulation. Overall, results with these silica gold nanoclusters suggest that they may be a potent nanoformulation against chemoresistant cancers.

Journal
ACS Molecular Pharmaceutics
Volume
15
Issue
7
Pagination
2698–2713
Publisher
ACS
ISSN
1543-8384
URL
https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b00218
Keywords
Akt, EGFR, epigallocatechin gallate, silica-gold nanoclusters, VEGFR2; ZD6474
Rights
Restricted Access
Peer Reviewed
Yes
Status
published
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