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Protease-Activatable Hybrid Nanoprobe for Tumor Imaging

机译：可蛋白酶激活的杂交纳米探针，用于肿瘤成像

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摘要

Tumor-associated proteases (TAPs), such as legumain, are actively involved in cancer progression; they have been used as biomarkers for diagnosis, prognosis, and drug targeting. As a result, in-vivo detection and trafficking of TAPs have attracted a great deal of attention. TAP-specific probes for in-vivo imaging, however, remain rare. A TAP-responsive hybrid nanoprobe system based on quantum dots (QD) and the fluorescence resonance energy transfer (FRET) effect is presented for the detection of legumain (asparaginyl endo-peptidase), which is overexpressed in many tumors. A novel hybrid construction method is developed for fabricating the nanoprobe, by which the strong heparin-protamine affinity is used for conjugation. The hybrid comprises two components: 1) low-molecular-weight heparin (LH)-modified QD, and 2) low-molecular-weight protamine (LMWP)-conjugated fluorescence quencher QSY21, through a legumain-cleavable linker. The hybrid nanoprobe (i.e., a FRET system) is self-assembled via the LH-LMWP affinity. The linker between LMWP and QSY21 is selectively cleaved by legumain, leading to QSY21 detachment and fluorescence recovery in the tumor. In-vivo imaging is successfully achieved in the colon tumor mouse model. Importantly, such a hybrid nanoprobe system is adaptable for the detection of other TAPs (e.g., matrix metalloproteinase -2) by using an established, corresponding sub-strate-peptide linker, thereby offering a universal platform for TAP detection and tumor imaging.
机译：肿瘤相关蛋白酶（TAP），如豆蔻因，积极参与癌症的发展。它们已被用作诊断，预后和靶向药物的生物标志物。结果，TAP的体内检测和贩运引起了极大的关注。但是，用于体内成像的TAP特异性探针仍然很少。提出了一种基于量子点（QD）和荧光共振能量转移（FRET）效应的TAP响应杂交纳米探针系统，用于检测在许多肿瘤中过表达的豆蔻因（天冬酰胺基内切肽酶）。开发了一种新颖的杂化构建方法来制造纳米探针，通过这种方法，强大的肝素-鱼精蛋白亲和力可用于缀合。该杂种包含两个成分：1）通过豆科素可裂解的连接子，低分子量肝素（LH）修饰的QD，和2）低分子量鱼精蛋白（LMWP）缀合的荧光猝灭剂QSY21。杂交纳米探针（即，FRET系统）通过LH-LMWP亲和力而自组装。 LMWP和QSY21之间的连接子被legumain选择性切割，导致QSY21分离和肿瘤中的荧光恢复。在结肠肿瘤小鼠模型中成功实现了体内成像。重要的是，这种杂合的纳米探针系统通过使用已建立的对应的底物-肽-肽接头而适用于检测其他TAP（例如基质金属蛋白酶-2），从而提供了用于TAP检测和肿瘤成像的通用平台。

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  • 来源
    《Advanced Functional Materials》 |2014年第34期|5443-5453|共11页
  • 作者

    Yaping Wang; Yifan Jiang; Meng Zhang; Jiao Tan; Jianming Liang; Huixin Wang; Yaping Li; Huining He; Victor C. Yang; Yongzhuo Huang;

  • 作者单位

    Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd, Shanghai 201203, China,Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmacy Tianjin Medical University, Tianjin 300070, China;

    Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd, Shanghai 201203, China;

    Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd, Shanghai 201203, China;

    Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd, Shanghai 201203, China;

    Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd, Shanghai 201203, China;

    Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd, Shanghai 201203, China;

    Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd, Shanghai 201203, China;

    Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmacy Tianjin Medical University, Tianjin 300070, China;

    Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmacy Tianjin Medical University, Tianjin 300070, China,University of Michigan College of Pharmacy 428 Church St, Ann Arbor, MI 48109-1065, USA;

    Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Rd, Shanghai 201203, China;

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