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Hapten-derivatized nanoparticle targeting and imaging of gene expression by multimodality imaging systems

Cancer Gene Therapy volume 16, pages 83–90 (2009)Cite this article

Abstract

Non-invasive gene monitoring is important for most gene therapy applications to ensure selective gene transfer to specific cells or tissues. We developed a non-invasive imaging system to assess the location and persistence of gene expression by anchoring an anti-dansyl (DNS) single-chain antibody (DNS receptor) on the cell surface to trap DNS-derivatized imaging probes. DNS hapten was covalently attached to cross-linked iron oxide (CLIO) to form a 39±0.5 nm DNS-CLIO nanoparticle imaging probe. DNS-CLIO specifically bound to DNS receptors but not to a control single-chain antibody receptor. DNS-CLIO (100 μM Fe) was non-toxic to both B16/DNS (DNS receptor positive) and B16/phOx (control receptor positive) cells. Magnetic resonance (MR) imaging could detect as few as 10% B16/DNS cells in a mixture in vitro. Importantly, DNS-CLIO specifically bound to a B16/DNS tumor, which markedly reduced signal intensity. Similar results were also shown with DNS quantum dots, which specifically targeted CT26/DNS cells but not control CT26/phOx cells both in vitro and in vivo. These results demonstrate that DNS nanoparticles can systemically monitor the expression of DNS receptor in vivo by feasible imaging systems. This targeting strategy may provide a valuable tool to estimate the efficacy and specificity of different gene delivery systems and optimize gene therapy protocols in the clinic.

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Acknowledgements

This work was supported by the National Research Program for Genomic Medicine (NRPGM), National Science Council, Taipei, Taiwan (NSC95-3112-B-037-001, NSC 95-2627-M-037-001) and the National Health Research Institutes (NHRI-EX96-9624SI). We acknowledge technical support from the Functional and Micro-Magnetic Resonance Imaging Center supported by the National Research Program for Genomic Medicine, National Science Council, Taiwan (NSC95-3112-B-001-009) and the National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center.

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  1. Y-M Wang and T-L Cheng: These authors contributed equally to this work.

Authors and Affiliations

  1. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    C-M Cheng, K-H Chuang & C-H Kao

  2. Faculty of Biomedical Laboratory Science, Kaohsiung Medical University, Kaohsiung, Taiwan

    P-Y Chu

  3. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    S R Roffler & B-M Chen

  4. Department of Chemistry, National Sun Yat-sen University, Kaohsiung, Taiwan

    W-L Tseng & J Shiea

  5. National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, Kaohsiung, Taiwan

    W-L Tseng, J Shiea & T-L Cheng

  6. Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan

    W-D Chang, Y-C Su & T-L Cheng

  7. Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan

    Y-M Wang

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  1. C-M Cheng
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Correspondence to Y-M Wang or T-L Cheng.

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Cheng, CM., Chu, PY., Chuang, KH. et al. Hapten-derivatized nanoparticle targeting and imaging of gene expression by multimodality imaging systems. Cancer Gene Ther 16, 83–90 (2009). https://doi.org/10.1038/cgt.2008.50

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