MMP-2-Activatable Photoacoustic Tumor Imaging Probes Based on Al- and Si-Naphthalocyanines
MMP-2-Activatable Photoacoustic Tumor Imaging Probes Based on Al- and Si-Naphthalocyanines
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DOI：
10.1021/acs.bioconjchem.1c00266
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发表时间：
2021-06-25
影响因子：
4.7
通讯作者：
Ohe, Kouichi
中科院分区：
文献类型：
--
作者：
Miki, Koji;Imaizumi, Naoto;Ohe, Kouichi
酶激活的光声探针是一种强大的造影剂，可以可视化特定酶过度表达的疾病。本研究以聚乙二醇为轴向配体，设计并合成了与基质金属蛋白酶-2(MMP2)反应的PLGLAG多肽序列偶联的铝和硅萘菁化合物(AINC和SINC)。AINC-多肽-聚乙二醇偶联物AINC-PEP-PEG在水中通过面对面的氢聚集形成二聚体相互作用，而基于SINC的偶联物SINC-PEP-PEG由于两个大的亲水性轴向配体几乎不相互作用。这两种结合物在水中形成了球形的纳米级自组装，在近红外光照射下产生光声波。MNC-多肽-聚乙二醇偶联物(M=AI，Si)与基质金属蛋白酶-2共同作用，能顺利地诱导PLGLAG序列的裂解，释放出亲水性的聚乙二醇组分，导致单核细胞聚集。通过比较680 nm和760 nm处PA信号强度的变化，发现与基质金属蛋白酶-2孵育后，光声信号强度比增加了3-5倍。我们证明了MNC-肽-聚乙二醇偶联物(M=Al，Si)可以作为可激活的光声探针应用于高表达MMP2的细胞株HT-1080的体外实验和荷瘤小鼠的体内光声成像。
Enzyme-activatable photoacoustic probes are powerful contrast agents to visualize diseases in which a specific enzyme is overexpressed. In this study, aluminum and silicon naphthalocyanines (AINc and SiNc, respectively) conjugated with matrix metalloprotease-2 (MMP-2)-responsive PLGLAG peptide sequence and poly(ethylene glycol) (PEG) as an axial ligand were designed and synthesized. AINc-peptide-PEG conjugates AINc-pep-PEG formed dimeric species interacting with each other through face-to-face H-aggregation in water, while SiNc-based conjugates SiNc-pep-PEG hardly interacted with each other because of the two bulky hydrophilic axial ligands. Both conjugates formed spherical nanometer-sized self-assemblies in water, generating photoacoustic waves under near-infrared photoirradiation. The treatment of MNc-peptide-PEG conjugates (M = AI, Si) with MMP-2 smoothly induced the cleavage of the PLGLAG sequence to release the hydrophilic PEG moiety, resulting in the aggregation of MNcs. By comparing the PA signal intensity changes at 680 and 760 nm, the photoacoustic signal intensity ratios were shown to be enhanced by 3-5 times after incubation with MMP-2. We demonstrated that MNc-peptide-PEG conjugates (M = Al, Si) could work as activatable photoacoustic probes in the in vitro experiment of MMP-2-overexpressed cell line HT-1080 as well as the in vivo photoacoustic imaging of HT-1080-bearing mice.