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

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• 作者：Fatemeh Ostadhossein ; Santosh K. Misra ; Prabuddha Mukherjee ; Alireza Ostadhossein ; Enrique Daza ; Saumya Tiwari ; Shachi Mittal ; Mark C. Gryka ; Rohit Bhargava and Dipanjan Pan
• 刊名：Small
• 出版年：2016
• 出版时间：November 9, 2016
• 年：2016
• 卷：12
• 期：42
• 页码：5845-5861
• 全文大小：4621K
• ISSN：1613-6829

文摘

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.