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

Nimisha Bhattarai, James Michael Mathis, Mi Chen, Rocío L. Pérez, Noureen Siraj, Paul K.S. Magut, Karen McDonough, Girija Sahasrabudhe, Isiah M. Warner

Research output: Contribution to journalArticle

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 vivo investigations 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 vitro therapeutic properties in vivo. These results corroborate the selective behavior of nanoGUMBOS and demonstrate their in vivo therapeutic effects, providing further insight into the possible use of these nanomaterials as potential chemotherapeutic agents.

Original languageEnglish
Pages (from-to)3837-3845
Number of pages9
JournalMolecular Pharmaceutics
Volume15
Issue number9
DOIs
StatePublished - 4 Sep 2018

Fingerprint

Nanostructures
Breast Neoplasms
Endocytosis
Neoplasms
Clathrin
Therapeutic Uses
Tumor Burden
Heterografts
Nanoparticles
Salts
rhodamine 6G
Therapeutics

Keywords

  • breast cancer
  • chemotherapy
  • group of uniform materials based on organic salts (GUMBOS)
  • nanoGUMBOS
  • nanomaterials
  • rhodamine 6G

Cite this

Bhattarai, N., Mathis, J. M., Chen, M., Pérez, R. L., Siraj, N., Magut, P. K. S., ... Warner, I. M. (2018). Endocytic Selective Toxicity of Rhodamine 6G nanoGUMBOS in Breast Cancer Cells. Molecular Pharmaceutics, 15(9), 3837-3845. https://doi.org/10.1021/acs.molpharmaceut.8b00339
Bhattarai, Nimisha ; Mathis, James Michael ; Chen, Mi ; Pérez, Rocío L. ; Siraj, Noureen ; Magut, Paul K.S. ; McDonough, Karen ; Sahasrabudhe, Girija ; Warner, Isiah M. / Endocytic Selective Toxicity of Rhodamine 6G nanoGUMBOS in Breast Cancer Cells. In: Molecular Pharmaceutics. 2018 ; Vol. 15, No. 9. pp. 3837-3845.
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Bhattarai, N, Mathis, JM, Chen, M, Pérez, RL, Siraj, N, Magut, PKS, McDonough, K, Sahasrabudhe, G & Warner, IM 2018, 'Endocytic Selective Toxicity of Rhodamine 6G nanoGUMBOS in Breast Cancer Cells', Molecular Pharmaceutics, vol. 15, no. 9, pp. 3837-3845. https://doi.org/10.1021/acs.molpharmaceut.8b00339

Endocytic Selective Toxicity of Rhodamine 6G nanoGUMBOS in Breast Cancer Cells. / Bhattarai, Nimisha; Mathis, James Michael; Chen, Mi; Pérez, Rocío L.; Siraj, Noureen; Magut, Paul K.S.; McDonough, Karen; Sahasrabudhe, Girija; Warner, Isiah M.

In: Molecular Pharmaceutics, Vol. 15, No. 9, 04.09.2018, p. 3837-3845.

Research output: Contribution to journalArticle

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T1 - Endocytic Selective Toxicity of Rhodamine 6G nanoGUMBOS in Breast Cancer Cells

AU - Bhattarai, Nimisha

AU - Mathis, James Michael

AU - Chen, Mi

AU - Pérez, Rocío L.

AU - Siraj, Noureen

AU - Magut, Paul K.S.

AU - McDonough, Karen

AU - Sahasrabudhe, Girija

AU - Warner, Isiah M.

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AB - 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 vivo investigations 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 vitro therapeutic properties in vivo. These results corroborate the selective behavior of nanoGUMBOS and demonstrate their in vivo therapeutic effects, providing further insight into the possible use of these nanomaterials as potential chemotherapeutic agents.

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