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Mono-dispersed high magnetic resonance sensitive magnetite nanocluster probe for detection of nascent tumors by magnetic resonance molecular imaging

  • Chunfu Zhang, PhD

      Affiliations

    • School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China
    • Corresponding Author InformationCorresponding author: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, P.R. China.
    • ,
  • Xuan Xie, MD

      Affiliations

    • School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China
    • ,
  • Sheng Liang, PhD

      Affiliations

    • Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China
    • ,
  • Mingli Li, MD

      Affiliations

    • School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China
    • ,
  • Yajie Liu, MS

      Affiliations

    • School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China
    • ,
  • Hongchen Gu, PhD

      Affiliations

    • School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China

Received 21 July 2011; accepted 22 November 2011. published online 26 December 2011.
Corrected Proof

Abstract 

Sensitive molecular imaging and detection of tumors or their supporting neovascularity require high-avidity, target-specific probes, which produce robust signal amplification compatible with a sensitive high-resolution imaging modality. In this context, we fabricated a high magnetic resonance (MR)-sensitive magnetite nanocluster (MNC) probe specific for tumor angiogenesis by assembly of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with (Mal)mPEG-PLA copolymer into cluster and subsequent encoding c(RGDyC) peptide on the cluster (RGD-MNC) for detection of nascent tumors. We found that RGD-MNC is highly sensitive (r2 = 464.94 s-1mM-1) and specific for αvβ3-positive cells. Both nascent (35 ± 6.6 mm3) and large tumors (256 ± 22.3 mm3) can be registered by RGD-MNC and detected by MR imaging (MRI), with the nascent tumors demonstrating more pronounced MR contrast. Immunohistochemical studies revealed that MR signal decrease was closely correlated with histological characteristics of tumors (microvessel density and αvβ3 expression levels) at different growth stages.

Graphical Abstract 

Due to its high sensitivity and specificity, both nascent and big tumors can be detected by RGD-MNC, and the MRI contrast is highly correlated with angiogenic vessel densities and αvβ3 integrin expression levels of tumors at different growth stages.

Key words: Nanocomposite, MRI, Molecular imaging, RGD peptide, αvβ3 integrin

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 This work was supported by Major State Basic Research Development Program of China (973 Program) (No. 2010CB834303), National Nature Science Foundation of China (30870682), Science and Technology Commission of Shanghai Municipal Government (10JC1408100), SRF for ROCS, SEM and Research Fund for the Doctoral Program of Higher Education of China (20090073120004).

 No conflict of interest was reported by the authors of this article.

PII: S1549-9634(11)00595-8

doi:10.1016/j.nano.2011.11.013

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