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

C. M. Cheng, P. Y. Chu, K. H. Chuang, S. R. Roffler, C. H. Kao, W. L. Tseng, J. Shiea, W. D. Chang, Y. C. Su, B. M. Chen, Yun-Ming Wang*, T. L. Cheng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalCancer Gene Therapy
Volume16
Issue number1
DOIs
StatePublished - 1 Jan 2009

Keywords

  • Anti-dansyl (DNS)
  • DNS-CLIO nanoparticle
  • DNS-derivatized imaging probes
  • DNS-quantum dots
  • Gene delivery system
  • Non-invasive imaging
  • Single-chain antibody

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