Activatable smart nanoprobe for sensitive endogenous MMP2 detection and fluorescence imaging-guided phototherapies
Activatable smart nanoprobe for sensitive endogenous MMP2 detection and fluorescence imaging-guided phototherapies
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可激活的智能纳米探针，用于敏感的内源性 MMP2 检测和荧光成像引导光疗
DOI：
10.1039/c9qi00002j
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发表时间：
2019-03-01
影响因子：
7
通讯作者：
Tang, Yu
中科院分区：
文献类型：
--
作者：
Hu, Binbin;Li, Pengyun;Tang, Yu
刺激激活治疗系统能够实现选择性成像和控制光疗，对于精确的癌症诊断和治疗至关重要。在此，我们设计了一种智能治疗纳米探针，由光敏剂（PS）、金纳米棒（aunr）和基质金属蛋白酶2 （MMP2）响应肽连接器组成。除了用于光动力治疗（PDT）外，PS还广泛用于荧光成像。光活性的时空调控对肿瘤治疗具有重要意义。在本研究中，由于PS和aunr之间存在福斯特共振能量转移（FRET），在循环过程中抑制了PS的荧光和O-1(2)的产生，避免了对正常组织的不良损害；然而，当癌细胞中过表达的MMP2切割肽连接体时，纳米探针可以被激活以进行靶向成像和选择性PDT。更重要的是，恢复的荧光可以成功地用于定量检测MMP2，检测限为29 pM，并照亮癌细胞，进一步指导协同激活的PDT/PTT（光热疗法）高效特殊杀伤癌细胞。这项研究可以帮助设计智能癌症相关的生物标志物激活治疗探针，用于分子传感和部位特异性癌症治疗。
A stimuli-activatable theranostic system enabling selective imaging and controlled phototherapies is highly essential for precise cancer diagnosis and treatment. Herein, we designed a smart theranostic nanoprobe that comprised a photosensitizer (PS), gold nanorods (AuNRs) and a matrix metalloproteinase 2 (MMP2)-responsive peptide linker. Apart from being applied for photodynamic therapy (PDT), PS has also been widely used for fluorescence imaging. Spatiotemporal control of the photoactivity of PS is of great importance for cancer theranostics. In the present work, due to the presence of Forster resonance energy transfer (FRET) between PS and AuNRs, the fluorescence and O-1(2) production of PS were suppressed during the circulation, avoiding adverse damage to normal tissues; however, the nanoprobe could be activated for targeted imaging and selective PDT when the peptide linker was cleaved by overexpressed MMP2 in cancer cells. More importantly, the restored fluorescence could be successfully used to quantitatively detect MMP2 with a detection limit of 29 pM and to light up cancer cells, further guiding synergistically activated PDT/PTT (photothermal therapy) for highly efficient and special killing of cancer cells. This study can help design smart cancer-related biomarker-activatable theranostic probes for molecular sensing and site-specific cancer treatment.