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用于肿瘤乏氧活体成像的靶向发光近红外聚合物纳米探针。

Targeted luminescent near-infrared polymer-nanoprobes for in vivo imaging of tumor hypoxia.

机构信息

Department of Hematology and Oncology, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.

出版信息

Anal Chem. 2011 Dec 1;83(23):9039-46. doi: 10.1021/ac201870b. Epub 2011 Nov 2.

DOI:10.1021/ac201870b
PMID:22007722
Abstract

Polystyrene nanoparticles (PS-NPs) were doped with an oxygen-sensitive near-infrared (NIR)-emissive palladium meso-tetraphenylporphyrin and an inert reference dye which are both excitable at 635 nm. The nanosensors were characterized with special emphasis on fundamental parameters such as absolute photoluminescence quantum yield and fluorescence lifetime. The PS-NPs were employed for ratiometric dual-wavelength and lifetime-based photoluminescent oxygen sensing. They were efficiently taken up by cultured murine alveolar macrophages, yielding a characteristic and reversible change in ratiometric response with decreasing oxygen concentration. This correlated with the cellular hypoxic status verified by analysis of hypoxia inducible factor-1α (HIF-1α) accumulation. In addition, the surface of PS-NPs was functionalized with polyethylene glycol (PEG) and the monoclonal antibody herceptin, and their binding to HER2/neu-overexpressing tumor cells was confirmed in vitro. First experiments with tumor-bearing mouse revealed a distinctive ratiometric response within the tumor upon hypoxic condition induced by animal sacrifice. These results demonstrate the potential of these referenced NIR nanosensors for in vitro and in vivo imaging that present a new generation of optical probes for oncology.

摘要

聚苯乙烯纳米粒子 (PS-NPs) 掺杂了氧敏近红外 (NIR) 发射钯 meso-四苯基卟啉和惰性参比染料,这两种染料都可以在 635nm 处被激发。纳米传感器的特点是特别强调基本参数,如绝对光致发光量子产率和荧光寿命。PS-NPs 被用于比率双波长和基于寿命的光致发光氧传感。它们被培养的鼠肺泡巨噬细胞有效摄取,导致比率响应随着氧浓度的降低而发生特征性和可逆的变化。这与通过缺氧诱导因子-1α (HIF-1α) 积累分析验证的细胞缺氧状态相关。此外,PS-NPs 的表面用聚乙二醇 (PEG) 和单克隆抗体赫赛汀进行功能化,并在体外证实了它们与过表达 HER2/neu 的肿瘤细胞的结合。在荷瘤小鼠的初步实验中,在动物牺牲引起的缺氧条件下,肿瘤内呈现出独特的比率响应。这些结果表明,这些参考近红外纳米传感器具有用于体外和体内成像的潜力,为肿瘤学提供了新一代光学探针。

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