Triglyceride-Rich Lipoprotein-Mediated Polymer Dots for Multimodal Imaging Interscapular Brown Adipose Tissue Capillaries.
Triglyceride-Rich Lipoprotein-Mediated Polymer Dots for Multimodal Imaging Interscapular Brown Adipose Tissue Capillaries.
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DOI：
10.1021/acsami.3c04525
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发表时间：
2023-06
影响因子：
9.5
通讯作者：
Jingru Li;Yixiao Guo;Panting Ren;Yufan Zhang;Ruijun Han;Liqin Xiong
中科院分区：
文献类型：
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作者：
Jingru Li;Yixiao Guo;Panting Ren;Yufan Zhang;Ruijun Han;Liqin Xiong
棕色脂肪组织（bat）已被确定为代谢紊乱的一个有希望的靶点。[18F]FDG-PET （FDG = fluorodeoxyglucose; PET =正电子发射断层扫描）主要用于BAT成像，但其局限性促使迫切需要结合多模态成像方法的新型功能探针。据报道，聚合物点（Pdots）无需额外的冷刺激即可显示快速的BAT成像。然而，Pdots成像BAT的机制尚不清楚。在这里，我们对成像机制进行了深入研究，发现Pdots可以与富含甘油三酯的脂蛋白（trl）结合。由于它们与trl的高亲和力，Pdots选择性地积聚在肩胛间棕色脂肪组织（iBATs）的毛细血管内皮细胞（ECs）中。与半衰期短的聚苯乙烯-共顺酐-异丙烯(PSMAC)-Pdots和亲脂性低的聚乙二醇(PEG)-Pdots相比，裸裸pdots具有良好的亲脂性，半衰期约为30 min， 5 min内毛细血管内皮细胞的吸收率高达94%，急性冷刺激后迅速增加。这些结果表明，Pdots在iBAT中的积累变化可以灵敏地反映iBAT的活性。基于这一机制，我们进一步开发了一种利用多模态Pdots检测iBAT活性并量化体内TRL摄取的策略。
Brown adipose tissues (BATs) have been identified as a promising target of metabolism disorders. [18F]FDG-PET (FDG = fluorodeoxyglucose; PET = positron emission tomography) has been predominantly employed for BAT imaging, but its limitations drive the urgent need for novel functional probes combined with multimodal imaging approaches. It has been reported that polymer dots (Pdots) display rapid BAT imaging without additional cold stimulation. However, the mechanism by which Pdots image BAT remains unclear. Here, we made an intensive study of the imaging mechanism and found that Pdots can bind to triglyceride-rich lipoproteins (TRLs). By virtue of their high affinity to TRLs, Pdots selectively accumulate in capillary endothelial cells (ECs) in interscapular brown adipose tissues (iBATs). Compared to poly(styrene-co-maleic anhydride)cumene terminated (PSMAC)-Pdots with a short half-life and polyethylene glycol (PEG)-Pdots with low lipophilicity, naked-Pdots have good lipophilicity, with a half-life of about 30 min and up to 94% uptake in capillary ECs within 5 min, increasing rapidly after acute cold stimulation. These results suggested that the accumulation changes of Pdots in iBAT can reflect iBAT activity sensitively. Based on this mechanism, we further developed a strategy to detect iBAT activity and quantify the TRL uptake in vivo using multimodal Pdots.