Journal
BIOMATERIALS
Volume 53, Issue -, Pages 229-238Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.02.093
Keywords
Molecular imaging; Intraoperative imaging; Molecular probe; Image-guided surgery; Photodynamic therapy
Funding
- National Natural Science Foundation of China (NSFC) [81471712, 81222019, 81125011, 81371614]
- 973 projects [2013CB733802, 2011CB707705]
- Ministry of Science and Technology of China [2011YQ030114, 2012ZX09102301, 2012BAK25B03]
- Beijing Natural Science Foundation [7132131, 7132123]
- Beijing Nova Program [Z121107002512010]
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Integrin alpha v beta 6 is widely upregulated in variant malignant cancers but is undetectable in normal organs, making it a promising target for cancer diagnostic imaging and therapy. Using streptavidin-biotin chemistry, we synthesized an integrin alpha v beta 6-targeted near-infrared phthalocyanine dye-labeled agent, termed Dye-SA-B-HK, and investigated whether it could be used for cancer imaging, optical imaging-guided surgery, and phototherapy in pancreatic cancer mouse models. Dye-SA-B-HK specifically bound to integrin alpha v beta 6 in vitro and in vivo with high receptor binding affinity. Using small-animal optical imaging, we detected subcutaneous and orthotopic BxPC-3 human pancreatic cancer xenografts in vivo. Upon optical image-guidance, the orthotopically growing pancreatic cancer lesions could be successfully removed by surgery. Using light irradiation, Dye-SA-B-HK manifested remarkable antitumor effects both in vitro and in vivo. F-18-FDG positron emission tomography (PET) imaging and ex vivo fluorescence staining validated the observed decrease in proliferation of treated tumors by Dye-DA-B-HK phototherapy. Tissue microarray results revealed overexpression of integrin alpha v beta 6 in over 95% cases of human pancreatic cancer, indicating that theranostic application of Dye-DA-B-HK has clear translational potential. Overall, the results of this study demonstrated that integrin alpha v beta 6-specific Dye-SA-B-HK is a promising theranostic agent for the management of pancreatic cancer. (C) 2015 Elsevier Ltd. All rights reserved.
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