Abstract
BackgroundGastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. How to recognize early gastric cancer cells is still a great challenge for early diagnosis and therapy of patients with gastric cancer. This study is aimed to develop one kind of multifunctional nanoprobes for in vivo targeted magnetofluorescent imaging of gastric cancer.MethodsBRCAA1 monoclonal antibody was prepared, was used as first antibody to stain 50 pairs of specimens of gastric cancer and control normal gastric mucous tissues, and conjugated with fluorescent magnetic nanoparticles with 50 nm in diameter, the resultant BRCAA1-conjugated fluorescent magnetic nanoprobes were characterized by transmission electron microscopy and photoluminescence spectrometry, as-prepared nanoprobes were incubated with gastric cancer MGC803 cells, and were injected into mice model loaded with gastric cancer of 5 mm in diameter via tail vein, and then were imaged by fluorescence optical imaging and magnetic resonance imaging, their biodistribution was investigated. The tissue slices were observed by fluorescent microscopy, and the important organs such as heart, lung, kidney, brain and liver were analyzed by hematoxylin and eosin (HE) stain method.ResultsBRCAA1 monoclonal antibody was successfully prepared, BRCAA1 protein exhibited over-expression in 64% gastric cancer tissues, no expression in control normal gastric mucous tissues, there exists statistical difference between two groups (P < 0.01). The BRCAA1-conjugated fluorescent magnetic nanoprobes exhibit very low-toxicity, lower magnetic intensity and lower fluorescent intensity with peak-blue-shift than pure FMNPs, could be endocytosed by gastric cancer MGC803 cells, could target in vivo gastric cancer tissues loaded by mice, and could be used to image gastric cancer tissues by fluorescent imaging and magnetic resonance imaging, and mainly distributed in local gastric cancer tissues within 12 h post-injection. HE stain analysis showed that no obvious damages were observed in important organs.ConclusionsThe high-performance BRCAA1 monoclonal antibody-conjugated fluorescent magnetic nanoparticles can target in vivo gastric cancer cells, can be used for simultaneous magnetofluorescent imaging, and may have great potential in applications such as dual-model imaging and local thermal therapy of early gastric cancer in near future.
Highlights
Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world
We found that BRCAA1 protein exhibited overexpression in 64% gastric cancer tissues, no expression in normal control gastric mucous tissues, as shown in Figure 1, there exists statistical difference between two group (P < 0.01)
This result is almost identical to our previous report [4,9,10,11], which highly suggest that BRCAA1 antigen may be selected as the potential target for most gastric cancer, if as-prepared nanoprobes may recognize 64% patients with early gastric cancer, it will be very useful for diagnosis and therapy of clinical gastric cancer patients
Summary
Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. How to recognize early gastric cancer cells is still a great challenge for early diagnosis and therapy of patients with gastric cancer. Gastric cancer is still the second most common cause of cancer-related death in the world, and remains difficult to cure because most patients present with advanced disease. In order to recognize early gastric cancer cells, we only select potential biomarkers associated with gastric cancer, and combine nanoparticles and molecular imaging techniques, try to find in vivo early gastric cancer cells by in vivo tumor targeted imaging. We predict that BRCAA1 protein may be one potential targeting molecule for in vivo gastric cancer cells
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