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pH-Activated Near-Infrared Fluorescence Nanoprobe Imaging Tumors by Sensing the Acidic Microenvironment

Authors

  • Cong Li,

    Corresponding author
    1. School of Pharmacy, Fudan University 826 Zhangheng Rd., Shanghai 201203 (PR China)
    • School of Pharmacy, Fudan University 826 Zhangheng Rd., Shanghai 201203 (PR China).
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  • Jinsong Xia,

    Corresponding author
    1. Department of Radiology, School of Medicine Johns Hopkins University 720 Rutland Ave., Baltimore 21205 (USA)
    • Department of Radiology, School of Medicine Johns Hopkins University 720 Rutland Ave., Baltimore 21205 (USA).
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  • Xunbin Wei,

    1. Cancer Hospital, Fudan University 399 Ling-Ling Road, Shanghai 200032 (PR China)
    2. Institutes of Biomedical Sciences, Fudan University 138 Yixueyuan Road, Shanghai 200032 (PR China)
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  • Huihui Yan,

    1. Department of Gastroenterology, Zhongshan Hospital Affiliated to Fudan University 130 DongAn Rd., Shanghai 200032 (PR China)
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  • Zhan Si,

    1. School of Pharmacy, Fudan University 826 Zhangheng Rd., Shanghai 201203 (PR China)
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  • Shenghong Ju

    1. Laboratory of Molecular Imaging, Department of Radiology Zhongda Hospital, Southeast University 87 Dingjiaqiao Rd., Nanjing 210009 (PR China)
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Abstract

Imaging tumors in their early stages is crucial to increase the surviving rate of cancer patients. Currently most fluorescence probes visualize the neoplasia by targeting the tumor-associated receptor over-expressed on the cancer cell membrane. However, the expression level of these receptors in vivo is hard to predict, which limits their clinical translation. Furthermore, the signal output of these receptor-targeting probes usually stays at a high level, which leads to a strong background signal in normal tissue due to non-specific binding. In contrast to receptors, characteristics of the tumor microenvironment – such as acidosis – are pervasive in almost all solid tumors and can be easily accessed. In this work, a novel biodegradable nanoprobe InNP1 that demonstrates pH-activated near-infrared (NIR) fluorescence in both human glioblastoma U87MG cancer cells in vitro and the subcutaneous U87MG tumor xenografts in vivo is developed. Bio-distribution, in vivo optical imaging, and autoradiography studies demonstrate that the pH-activated NIR fluorescence is the dominant factor responsible for the high tumor/normal tissue (T/N) ratio of InNP1 in vivo. Overall, the work provides a nanoprobe prototype to visualize the solid tumor in vivo with high sensitivity and minimal systemic toxicity by sensing the tumor acidic microenvironment.

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