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New strategy of efficient inhibition of cancer cells by carborane carboxylic acid–CdTe nanocomposites

  • Chunhui Wu, PhD

      Affiliations

    • State Key Lab of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing 210096, China
    • ,
  • Lixin Shi, PhD

      Affiliations

    • Department of Chemistry and Biochemistry, California State University–Los Angeles, Los Angeles, California, USA
    • ,
  • Qingning Li, PhD

      Affiliations

    • State Key Lab of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing 210096, China
    • ,
  • Hui Jiang, PhD

      Affiliations

    • State Key Lab of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing 210096, China
    • ,
  • Matthias Selke, PhD

      Affiliations

    • Department of Chemistry and Biochemistry, California State University–Los Angeles, Los Angeles, California, USA
    • ,
  • Hong Yan, PhD

      Affiliations

    • State Key Lab of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing National lab of Microstructures, Nanjing University, Nanjing, Jiangsu, China
    • ,
  • Xuemei Wang, PhD

      Affiliations

    • State Key Lab of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing 210096, China
    • Corresponding Author InformationCorresponding author: State Key Lab of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Sipailou 2, Nanjing 210096, China.

Received 30 May 2011; accepted 27 October 2011. published online 16 November 2011.
Corrected Proof

Abstract 

Nanoconjugates composed of drug molecules encapsulated in quantum dots (QDs) attract enormous attention due to their promising bioimaging and biomedical applications. Here, the anticancer efficiency of potential pharmacophore agents (o-carborane (Cb), o-carborane-C-carboxylic acid (Cbac1), and o-carborane-C(1)C(2)-dicarboxylic acid (Cbac2) coupling with cadmium telluride QDs capped with cysteamine (CA-CdTe QDs)) have been explored. Compared with free CA-CdTe QDs, the composites consisting of Cbac1/Cbac2 and safe-dosage QDs can greatly improve the inhibition efficiency toward SMMC-7721 hepatocellular carcinoma cells with the aid of our real-time cell bioelectronic sensing system and the MTT assay. The enhanced cytotoxicity correlates with increased intracellular reactive oxygen species generation and cell apoptosis. Confocal laser scanning fluorescent microscopy shows improved cellular uptake and drug distribution of the Cbac1/Cbac2-CdTe QDs nanoconjugates. This work raises the possibility that the carborane pharmacophore in combination with QDs or other anticancer drugs may be viable for efficient cancer diagnosis and chemotherapy.

Graphical Abstract

In this contribution, the specific interactions of carborane pharmacophore agents, namely carborane–carboxylic acid derivatives (denoted as Cbac1 and Cbac2), with cadmium telluride quantum dots capped with cysteamine (CA-CdTe QDs) are explored. The corresponding carborane–carboxylic acid derivatives–CdTe nanoconjugates exhibit synergistic inhibition on target cancer cells, raising the possibility of carborane anticancer agents in combination with safe-dosage QDs for cancer chemotherapy.

Key words: Carborane carboxylic derivatives, Quantum dots, Nanocomposites, Cancer cell inhibition

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 The research is supported by the National Basic Research Program of China (2010CB732404), National Natural Science Foundation of China (21175020 and 20925104), the Natural Science Foundation of Jiangsu Province (BK2008149 and BK2010052). L.S. and M.S. gratefully acknowledge support from the United States National Institutes of Health–National Institute of General Medical Science (5SC1GM084776) and the National Science Foundation–Centers of Research Excellence in Science and Technology program (HRD0932421). C.W. acknowledges support by the Open Research Fund (2011E09) of the State Key Laboratory of Bioelectronics, Southeast University.

PII: S1549-9634(11)00517-X

doi:10.1016/j.nano.2011.10.011

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