A series of integrin αvβ3 targeting BODIPY-RGD conjugate were designed and synthesized. Their in vitro and in vivo fluorescence imaging behaviors were investigated. The small molecule compound was designed as an optical imaging near-infrared fluorescent dye which was combined RGD peptide with the meso-amide BODIPYs using succinic moiety as a spacer. The construction alleviated the traditional BODIPY problems including poor water solubility, aggregate caused quench (ACQ) effect, low biocompatibility, etc. In cellular research, BDP-RGD-2 showed rapid, selective uptake in 3 highly expressing integrin αvβ3 cell lines MDA-MB-231, A549, U87MG at different extent rather than an integrin αvβ3 low level expression cell MCF-7. In animal study, fluorescence imaging of U87MG model targeted by BDP-RGD-2 displayed a highest tumor uptake level and T/N ratio up to 6 h after tail-intravenous injection, which demonstrated BDP-RGD-2 was a promising probe for tracing integrin αvβ3 overexpressing tumors.

中文翻译：

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靶向整合素 αvβ3 的新型 BODIPY 荧光探针的合成和评价用于癌症诊断


设计合成了一系列靶向 BODIPY-RGD 偶联物的整合素 αvβ3。研究了它们的体外和体内荧光成像行为。小分子化合物被设计为光学成像近红外荧光染料，其使用琥珀酸部分作为间隔物将 RGD 肽与内消旋酰胺 BODIPYs 结合。该结构缓解了传统的 BODIPY 问题，包括水溶性差、骨料引起淬火 （ACQ） 效应、生物相容性低等。在细胞研究中，BDP-RGD-2 在 3 种高表达整合素 αvβ3 细胞系 MDA-MB-231、A549、U87MG 中表现出不同程度的快速选择性摄取，而不是整合素 αvβ3 低水平表达细胞 MCF-7。在动物研究中，BDP-RGD-2 靶向的 U87MG 模型的荧光成像显示，在静脉尾部注射后长达 6 h 的肿瘤摄取水平和 T/N 比值最高，这表明 BDP-RGD-2 是追踪整合素 αvβ3 过表达肿瘤的有前途的探针。