Novel peptide targeting integrin αvβ3-rich tumor cells by magnetic resonance imaging
Corresponding Author
Guoqiu Wu MD, PhD
Center of Clinical Laboratory Medicine of Zhongda Hospital, Institute of Biotechnology and Clinical Pharmacy, Southeast University, Nanjing, China
The first two authors contributed equally to this study.
Guoqiu Wu, Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University. Dingjiaqiao 87, Nanjing 210009, China
Naifeng Liu, Institute of Cardiovascular Disease of Zhongda Hospital, Southeast University. Dingjiaqiao 87, Nanjing 210009, China
Search for more papers by this authorXiaodong Wang MD
Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
The first two authors contributed equally to this study.
Search for more papers by this authorGang Deng MD, PhD
Laboratory of Molecular Imaging, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China
Search for more papers by this authorLinyuan Wu RS
Department of Biological Science and Medical Engineering, Southeast University, Nanjing, China
Search for more papers by this authorShenghong Ju MD, PhD
Laboratory of Molecular Imaging, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China
Search for more papers by this authorGaojun Teng MD, PhD
Laboratory of Molecular Imaging, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China
Search for more papers by this authorYuyu Yao MD, PhD
Institute of Cardiovascular Eisease of Zhongda Hospital, Southeast University, Nanjing, China
Search for more papers by this authorXiyong Wang MS
Medical School of Southeast University, Nanjing, China
Search for more papers by this authorCorresponding Author
Naifeng Liu MD, PhD
Institute of Cardiovascular Eisease of Zhongda Hospital, Southeast University, Nanjing, China
Guoqiu Wu, Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University. Dingjiaqiao 87, Nanjing 210009, China
Naifeng Liu, Institute of Cardiovascular Disease of Zhongda Hospital, Southeast University. Dingjiaqiao 87, Nanjing 210009, China
Search for more papers by this authorCorresponding Author
Guoqiu Wu MD, PhD
Center of Clinical Laboratory Medicine of Zhongda Hospital, Institute of Biotechnology and Clinical Pharmacy, Southeast University, Nanjing, China
The first two authors contributed equally to this study.
Guoqiu Wu, Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University. Dingjiaqiao 87, Nanjing 210009, China
Naifeng Liu, Institute of Cardiovascular Disease of Zhongda Hospital, Southeast University. Dingjiaqiao 87, Nanjing 210009, China
Search for more papers by this authorXiaodong Wang MD
Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
The first two authors contributed equally to this study.
Search for more papers by this authorGang Deng MD, PhD
Laboratory of Molecular Imaging, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China
Search for more papers by this authorLinyuan Wu RS
Department of Biological Science and Medical Engineering, Southeast University, Nanjing, China
Search for more papers by this authorShenghong Ju MD, PhD
Laboratory of Molecular Imaging, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China
Search for more papers by this authorGaojun Teng MD, PhD
Laboratory of Molecular Imaging, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China
Search for more papers by this authorYuyu Yao MD, PhD
Institute of Cardiovascular Eisease of Zhongda Hospital, Southeast University, Nanjing, China
Search for more papers by this authorXiyong Wang MS
Medical School of Southeast University, Nanjing, China
Search for more papers by this authorCorresponding Author
Naifeng Liu MD, PhD
Institute of Cardiovascular Eisease of Zhongda Hospital, Southeast University, Nanjing, China
Guoqiu Wu, Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University. Dingjiaqiao 87, Nanjing 210009, China
Naifeng Liu, Institute of Cardiovascular Disease of Zhongda Hospital, Southeast University. Dingjiaqiao 87, Nanjing 210009, China
Search for more papers by this authorAbstract
Purpose:
To investigate the targeting activity of the peptide (named P1c) derived from connective tissue growth factor (CTGF) to αvβ3-rich tumor cells.
Materials and Methods:
P1c was synthesized and conjugated with ultrasuperparamagnetic iron oxide particles (USPIOs) coated with meso-2,3-dimercaptosuccinic acid (DMSA). The specific binding activity of P1c-USPIOs to αvβ3 was verified by solid phase binding assay. The combination of P1c-USPIOs with a human primary liver cancer cell (Bel 7402) with αvβ3-positive expression and uptake of P1c-USPIOs by cells was investigated by Prussian blue staining, transmission electron microscopy (TEM), and magnetic resonance imaging (MRI). The targeting activity of the probe in vivo was also evaluated using a small-animal tumor model by MRI.
Results:
The cell uptake of P1c-USPIOs was observed in a dose-dependent manner, whereas no significant particle uptake was found in the plain USPIOs group. The differences on T2*-weighted imaging were also found by MRI and the signal intensity (SI) was statistically reduced after coculture of Bel 7402 cells with P1c-USPIOs at a concentration of 20–80 μg/mL compared with plain USPIOs (P < 0.05). The in vivo study showed that the signal reduction was distributed mainly in the periphery and some central areas of the tumor. The tumor-to-muscle CNR (contrast-to-noise ratio) at 12 hours after the administration of the P1c-USPIOs was statistically significantly different compared to those at 0 hour, 1 hour, or the plain USPIO group (P < 0.05).
Conclusion:
The peptide P1c might be a good candidate as a targeting carrier for drugs or tracers. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.
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