Targeting of EGFR, VEGFR2, and Akt by Engineered Dual Drug Encapsulated Mesoporous Silica-Gold Nanoclusters Sensitizes Tamoxifen-Resistant Breast Cancer

B. N.Prashanth Kumar, Nagaprasad Puvvada, Shashi Rajput, Siddik Sarkar, Madhusudan Kr Mahto, Murali Yallapu, Amita Pathak, Luni Emdad, Swadesh K. Das, Rui L. Reis, S. C. Kundu, Paul B. Fisher, Mahitosh Mandal

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2698-2713
Number of pages16
JournalMolecular Pharmaceutics
Volume15
Issue number7
DOIs
StatePublished - Jul 2 2018

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Tamoxifen
Silicon Dioxide
Gold
Breast Neoplasms
Pharmaceutical Preparations
Neoplasms
Vascular Endothelial Growth Factor Receptor-2
Epidermal Growth Factor Receptor
Disease-Free Survival
Therapeutics
Research Personnel
Apoptosis
Phenotype
Mutation
Survival
Mortality
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Targeting of EGFR, VEGFR2, and Akt by Engineered Dual Drug Encapsulated Mesoporous Silica-Gold Nanoclusters Sensitizes Tamoxifen-Resistant Breast Cancer. / Kumar, B. N.Prashanth; Puvvada, Nagaprasad; Rajput, Shashi; Sarkar, Siddik; Mahto, Madhusudan Kr; Yallapu, Murali; Pathak, Amita; Emdad, Luni; Das, Swadesh K.; Reis, Rui L.; Kundu, S. C.; Fisher, Paul B.; Mandal, Mahitosh.

In: Molecular Pharmaceutics, Vol. 15, No. 7, 02.07.2018, p. 2698-2713.

Research output: Contribution to journalArticle

Kumar, BNP, Puvvada, N, Rajput, S, Sarkar, S, Mahto, MK, Yallapu, M, Pathak, A, Emdad, L, Das, SK, Reis, RL, Kundu, SC, Fisher, PB & Mandal, M 2018, 'Targeting of EGFR, VEGFR2, and Akt by Engineered Dual Drug Encapsulated Mesoporous Silica-Gold Nanoclusters Sensitizes Tamoxifen-Resistant Breast Cancer', Molecular Pharmaceutics, vol. 15, no. 7, pp. 2698-2713. https://doi.org/10.1021/acs.molpharmaceut.8b00218
Kumar, B. N.Prashanth ; Puvvada, Nagaprasad ; Rajput, Shashi ; Sarkar, Siddik ; Mahto, Madhusudan Kr ; Yallapu, Murali ; Pathak, Amita ; Emdad, Luni ; Das, Swadesh K. ; Reis, Rui L. ; Kundu, S. C. ; Fisher, Paul B. ; Mandal, Mahitosh. / Targeting of EGFR, VEGFR2, and Akt by Engineered Dual Drug Encapsulated Mesoporous Silica-Gold Nanoclusters Sensitizes Tamoxifen-Resistant Breast Cancer. In: Molecular Pharmaceutics. 2018 ; Vol. 15, No. 7. pp. 2698-2713.
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