Cetuximab-modified CuS nanoparticles integrating near-infrared-II-responsive photothermal therapy and anti-vessel treatment
Cetuximab-modified CuS nanoparticles integrating near-infrared-II-responsive photothermal therapy and anti-vessel treatment
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DOI：
10.2147/ijn.s175334
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发表时间：
2018-01-01
影响因子：
8
通讯作者：
Lao, Xingzhen
中科院分区：
文献类型：
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作者：
Li, Bin;Jiang, Zhongyin;Lao, Xingzhen
背景：光热疗法（PTT）因其无创性和高疗效而受到广泛关注。PTT试剂和近红外激光器是PTT的重要组成部分。然而，大多数PTT药物均由重金属组成，具有严重的细胞毒性和副作用，且近红外辐射的高剂量往往会损伤正常组织，从而限制了PTT的临床应用。目的：探索新的视角，使更多的PTT药物富集到肿瘤中，近红外激光照射在PTT中的衰变至关重要。方法：本研究将靶向EGFR的抗血管生成抗体西妥昔单抗（cetuximab, Ab）修饰在CuS NPs （CuS-Ab NPs）上，改善CuS NPs在肿瘤中的聚集。结果：细胞摄取数据和生物分布结果显示CuS-Ab NPs在肿瘤中的积累相当，从而降低了正常组织中的细胞毒性和副作用。更重要的是，免疫组织化学染色显示，cu -Ab NPs中Ab的修饰显著抑制了肿瘤血管的形成和进展。引入抗血管治疗需要cu - ab NPs提供弱PTT，这意味着需要少量的激光能量，不可避免地对正常组织造成可忽略不计的损伤。结论：因此，我们量身定制的cu - ab NPs具有良好的临床应用潜力。
Background: Photothermal therapy (PTT) has received extensive attention owing to its non-invasive nature and highly therapeutic outcomes. PTT agents and near-infrared (NIR) laser are essential elements in PTT. However, most PTT agents are composed of heavy metals, characterized by serious cytotoxicity and side effects, and NIR irradiation often damages normal tissue owing to the high dose, thus limiting the clinical application of PTT.Purpose: In this regard, exploring new perspectives enabling more PTT agents to be enriched into the tumor and NIR laser irradiation decay in PTT is vital.Methods: In this study, cetuximab (Ab), an anti-angiogenic antibody which targets the EGFR, was modified on CuS NPs (CuS-Ab NPs) to improve the aggregation of CuS NPs in the tumor.Results: The cellular uptake data and the biodistribution results showed comparable accumulation of CuS-Ab NPs in tumor, thus decreasing the cytotoxicity and side effects in normal tissues. More importantly, the modification of Ab in CuS-Ab NPs impressively inhibited the formation and progression of tumor vessels, as demonstrated by immunohistochemistry staining. The introduction of anti-vessel treatment requires CuS-Ab NPs to provide weak PTT, which means that a small amount of laser energy is required, inevitably causing negligible damage to normal tissue.Conclusion: Therefore, our tailor-made CuS-Ab NPs have promising potential in clinical applications.