A cross-talk EGFR/VEGFR-targeted bispecific nanoprobe for magnetic resonance/near-infrared fluorescence imaging of color

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Research Letter

A cross-talk EGFR/VEGFR-targeted bispecific nanoprobe for magnetic resonance/near-infrared fluorescence imaging of colorectal cancer Qian Wang, and Xinming Zhao, Department of Diagnostic Imaging, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China Hao Yan, and Feiyu Kang, School of Materials Science and Engineering & Graduate School at Shenzhen, Tsinghua University, Beijing 100190, China Zhangfu Li, Yanyan Qiao, and Dan Li, State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China Address all correspondence to Dan Li and Xinming Zhao at [email protected] and [email protected] (Received 15 May 2018; accepted 29 June 2018)

Abstract Due to the lack of an effective and noninvasive screening tool, the early diagnosis of colorectal cancer (CRC) is currently difficult. For the early diagnosis of CRC, we have developed Fe3O4-Dye800-single chain fragment variable (ScFv)egfr/vegfr nanoprobes. ScFvegfr/vegfr (ScFv2) conjugated onto Fe3O4 nanoprobes efficiently recognized CRC tumors in vitro and in vivo. Near-infrared fluorescence imaging modalities such as Dye800 were utilized simultaneously with magnetic resonance to enhance detection efficiency. Fe3O4-Dye800-ScFv2 successfully detected tiny CRC tumors; the synergistic ScFv2 successfully enhanced CRC targeting. Thus, Fe3O4-Dye800-ScFv2 nanoprobes may represent a new molecular imaging strategy for the early detection of CRC.

Introduction Colorectal cancer (CRC) is the third-most common malignant cancer worldwide, which is one of the most common causes of cancer-related deaths in America and Europe.[1] Approximately 30% of patients are diagnosed with metastatic disease at present, which results in poor prognosis and markedly shortens their lifespan.[2] The most important reason for this is the lack of a noninvasive and efficient screening tool for the early detection of CRC. Additionally, usual radiology examinations are not specific enough and intestinal endoscopy is unfavorable for the patient. Thus, the early diagnosis of CRC and even precancerous CRC lesions will revolutionize diagnosis and treatment guidelines. A novel “cross-talk” strategy that enhances the targeting capability by combining MRI and nearinfrared fluorescence (NIRF) could make the early diagnosis of CRC possible. CRC is a hypervascular tumor showing prominent enhanced permeability and retention (EPR) effects, resulting in nanoparticles (NPs) being easily retained in tumor tissues; the full advantage of this fact can be taken for nano-imaging and while using nanocarriers.[3] Magnetic iron oxide NPs have been demonstrated to be an irreplaceable choice as novel agents for cancer diagnosis using magnetic resonance imaging (MRI), because of their delicate surface modification and controllable particle size. Especially for CRC, magnetic iron oxide NPs can be used as T2 contrast agents that can generate a n