title: Defined Host-Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer.
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 IC50of 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.
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 W. Springfield Ave., Urbana, IL, 61801, USA.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ostadhossein
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 W. Springfield Ave., Urbana, IL, 61801, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Misra
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 W. Springfield Ave., Urbana, IL, 61801, USA.
authors.forename: Prabuddha
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ostadhossein
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 W. Springfield Ave., Urbana, IL, 61801, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Daza
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 W. Springfield Ave., Urbana, IL, 61801, USA.
authors.forename: Saumya
authors.initials: S
authors.lastname: Tiwari
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 W. Springfield Ave., Urbana, IL, 61801, USA.
authors.forename: Shachi
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 W. Springfield Ave., Urbana, IL, 61801, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Gryka
authors.affiliation: Departments of Bioengineering, Electrical and Computer Engineering, Chemical and Biomolecular Engineering, Chemistry, and Mechanical Science and Engineering, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 1304 W. Springfield Ave., Urbana, IL, 61801, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhargava
authors.affiliation: Carle Foundation Hospital, 502 N. Busey St., Urbana, IL, 61801, USA.|Departments of Bioengineering and Materials Science and Engineering, Beckman Institute for Advanced Science and Technology, Institute for Sustainability in Energy and Environment, 502 N. Busey St., Urbana, IL, 61801, USA.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Pan
keywords: STAT-3; breast cancer; host-guest chemistry; nanoparticles; vibrational spectroscopic imaging