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Endocytic Selective Toxicity of Rhodamine 6G nanoGUMBOS in Breast Cancer Cells

Authors :
Bhattarai, Nimisha
Mathis, J. Michael
Chen, Mi
Pérez, Rocío L.
Siraj, Noureen
Magut, Paul K. S.
McDonough, Karen
Sahasrabudhe, Girija
Warner, Isiah M.
Source :
Molecular Pharmaceutics; July 2018, Vol. 15 Issue: 9 p3837-3845, 9p
Publication Year :
2018

Abstract

Herein, we report on the role of endocytosis in the selective chemotherpeutic toxicity of rhodamine 6G (R6G) based nanomaterials, i.e., nanoGUMBOS, that are derived from a group of uniform materials based on organic salts (GUMBOS). Evaluation of cellular uptake in the presence and absence of endocytosis inhibitors suggests nanoGUMBOS internalization via clathrin-mediated endocytosis in cancer cells and reveals lack of endocytic internalization in normal cells. Results from characterization of these nanomaterials suggest that endocytic internalization in cancer cells leads to nanoGUMBOS dissociation within the endosomal environment. This ultimately results in selective cytotoxicity of the nanoGUMBOS for cancer cells with no toxicity toward normal cells under examined conditions. Following examination of the selectivity mechanism, in vivoinvestigations were performed to examine potential therapeutic properties of these nanoparticles. Remarkably, nanoGUMBOS treatment using a mouse xenograft model reduced the tumor volume by 50% suggesting retention of in vitrotherapeutic properties in vivo. These results corroborate the selective behavior of nanoGUMBOS and demonstrate their in vivotherapeutic effects, providing further insight into the possible use of these nanomaterials as potential chemotherapeutic agents.

Details

Language :
English
ISSN :
15438384 and 15438392
Volume :
15
Issue :
9
Database :
Supplemental Index
Journal :
Molecular Pharmaceutics
Publication Type :
Periodical
Accession number :
ejs45961808
Full Text :
https://doi.org/10.1021/acs.molpharmaceut.8b00339