Hypoxia-specific ultrasensitive detection of tumours and cancer cells in vivo

Xianchuang Zheng,Baorui Liu,Hui Mao,Xiqun Jiang,Wei Wu,Xin Wang

doi:10.1038/ncomms6834

Xianchuang Zheng, Baorui Liu + Show 4 more

Open Access

https://doi.org/10.1038/ncomms6834

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Abstract

Highly sensitive and specific non-invasive molecular imaging methods are particularly desirable for the early detection of cancers. Here we report a near-infrared optical imaging probe highly specific to the hypoxic tumour microenvironment to detect tumour and cancer cells with the sensitivity to a few thousands cancer cells. This oxygen-sensitive, near-infrared emitting and water-soluble phosphorescent macromolecular probe can not only report the hypoxic tumour environment of various cancer models, including metastatic tumours in vivo, but can also detect a small amount of cancer cells before the formation of the tumour based on the increased oxygen consumption during cancer cell proliferation. Thus, the reported hypoxia-sensitive probe may offer an imaging tool for characterizing the tumour microenvironment in vivo, detecting cancer cells at a very early stage of tumour development and lymph node metastasis.

Highlights

Sensitive and specific non-invasive molecular imaging methods are desirable for the early detection of cancers
Tumour hypoxia leads to an increased level of regulatory transcription factors such as hypoxia inducible factor 1a (HIF-1a) to upregulate the expression of genes associated with tumour initiation, malignant progression, metastasis and resistance to chemotherapy and radiotherapy[7,8,9,10,11]
Reports on the development of non-invasive hypoxia imaging probes are typically based on nitroimidazole compounds that can be used for positron emission tomography imaging and magnetic resonance imaging[12,13]

Summary

Introduction

Sensitive and specific non-invasive molecular imaging methods are desirable for the early detection of cancers. The photon counts s À 1 measured in the tumour region at different time points (Fig. 3b) revealed that the phosphorescence intensity in the tumour region increased rapidly after the injection of the probe. (d) The averaged signal intensities of Ir moiety (red) and NIR-797 moiety (purple) in the tumours at different time points after i.v. injection of Ir-PVP-N797.

Results

Conclusion