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Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer
Author(s) -
Ostadhossein Fatemeh,
Misra Santosh K.,
Mukherjee Prabuddha,
Ostadhossein Alireza,
Daza Enrique,
Tiwari Saumya,
Mittal Shachi,
Gryka Mark C.,
Bhargava Rohit,
Pan Dipanjan
Publication year - 2016
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201601161
Subject(s) - internalization , chemistry , in vivo , niclosamide , nanocarriers , bioavailability , stat protein , stat3 , in vitro , aqueous solution , biophysics , combinatorial chemistry , nanotechnology , drug delivery , biochemistry , pharmacology , organic chemistry , phosphorylation , materials science , cell , biology , ecology , microbiology and biotechnology
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 IC 50 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.