Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer

Fatemeh Ostadhossein, Santosh K. Misra, Prabuddha Mukherjee, Alireza Ostadhossein, Enrique Daza, Saumya Tiwari, Shachi Mittal, Mark C. Gryka, Rohit Bhargava, Dipanjan Pan

Research output: Contribution to journalArticle

Abstract

Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host–guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization. Extensive physicochemical characterizations confirm successful synthesis. Subsequently, the host–guest chemistry of niclosamide and cucurbit[6]uril is studied experimentally and computationally. In vitro assessments in human breast cancer cells indicate approximately twofold enhancement in IC50 of drug. Fourier transform infrared and fluorescence imaging demonstrate efficient cellular internalization. Furthermore, the catalytic biodegradation of the nanoplatforms occur upon exposure to human myeloperoxidase in short time. In vivo studies on athymic mice with MCF-7 xenograft indicate the size of tumor in the treatment group is half of the controls after 40 d. Immunohistochemistry corroborates the downregulation of STAT-3 phosphorylation. Overall, the host–guest chemistry on nanocarbon acts as a novel arsenal for STAT-3 inhibition.

Original languageEnglish (US)
Pages (from-to)5845-5861
Number of pages17
JournalSmall
Volume12
Issue number42
DOIs
StatePublished - Nov 9 2016

Fingerprint

Transcription Factor 3
STAT3 Transcription Factor
Transcription factors
Niclosamide
Transducers
Solubility
Neoplasms
Pharmaceutical Preparations
Biological Availability
Carbon
Arsenals
Phosphorylation
Neoplastic Stem Cells
Optical Imaging
Fourier Analysis
Biodegradation
Stem cells
Heterografts
Nude Mice
Nanoparticles

Keywords

  • STAT-3
  • breast cancer
  • host–guest chemistry
  • nanoparticles
  • vibrational spectroscopic imaging

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Engineering (miscellaneous)

Cite this

Ostadhossein, F., Misra, S. K., Mukherjee, P., Ostadhossein, A., Daza, E., Tiwari, S., ... Pan, D. (2016). Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer. Small, 12(42), 5845-5861. https://doi.org/10.1002/smll.201601161

Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer. / Ostadhossein, Fatemeh; Misra, Santosh K.; Mukherjee, Prabuddha; Ostadhossein, Alireza; Daza, Enrique; Tiwari, Saumya; Mittal, Shachi; Gryka, Mark C.; Bhargava, Rohit; Pan, Dipanjan.

In: Small, Vol. 12, No. 42, 09.11.2016, p. 5845-5861.

Research output: Contribution to journalArticle

Ostadhossein, F, Misra, SK, Mukherjee, P, Ostadhossein, A, Daza, E, Tiwari, S, Mittal, S, Gryka, MC, Bhargava, R & Pan, D 2016, 'Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer', Small, vol. 12, no. 42, pp. 5845-5861. https://doi.org/10.1002/smll.201601161
Ostadhossein F, Misra SK, Mukherjee P, Ostadhossein A, Daza E, Tiwari S et al. Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer. Small. 2016 Nov 9;12(42):5845-5861. https://doi.org/10.1002/smll.201601161
Ostadhossein, Fatemeh ; Misra, Santosh K. ; Mukherjee, Prabuddha ; Ostadhossein, Alireza ; Daza, Enrique ; Tiwari, Saumya ; Mittal, Shachi ; Gryka, Mark C. ; Bhargava, Rohit ; Pan, Dipanjan. / Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer. In: Small. 2016 ; Vol. 12, No. 42. pp. 5845-5861.
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