Interface-Targeting Strategy Enables Two-Photon Fluorescent Lipid Droplet Probes for High-Fidelity Imaging of Turbid Tissues and Detecting Fatty Liver,ACS Applied Materials & Interfaces

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Interface-Targeting Strategy Enables Two-Photon Fluorescent Lipid Droplet Probes for High-Fidelity Imaging of Turbid Tissues and Detecting Fatty Liver
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-03-09 00:00:00 , DOI: 10.1021/acsami.8b00278
Lifang Guo ₁ , Minggang Tian ₁ , Ruiqing Feng ₁ , Ge Zhang ₁ , Ruoyao Zhang ₁ , Xuechen Li ₁ , Zhiqiang Liu ₁ , Xiuquan He ₂ , Jing Zhi Sun ₃ , Xiaoqiang Yu ₁

Affiliation

Lipid droplets (LDs) with unique interfacial architecture not only play crucial roles in protecting a cell from lipotoxicity and lipoapoptosis but also closely relate with many diseases such as fatty liver and diabetes. Thus, as one of the important applied biomaterials, fluorescent probes with ultrahigh selectivity for in situ and high-fidelity imaging of LDs in living cells and tissues are critical to elucidate relevant physiological and pathological events as well as detect related diseases. However, available probes only utilizing LDs’ waterless neutral cores but ignoring the unique phospholipid monolayer interfaces exhibit low selectivity. They cannot differentiate neutral cores of LDs from intracellular other lipophilic microenvironments, which results in extensively cloud-like background noise and severely limited their bioapplications. Herein, to design LD probes with ultrahigh selectivity, the exceptional interfacial architecture of LDs is considered adequately and thus an interface-targeting strategy is proposed for the first time. According to the novel strategy, we have developed two amphipathic fluorescent probes (N-Cy and N-Py) by introducing different cations into a lipophilic fluorophore (nitrobenzoxadiazole (NBD)). Consequently, their cationic moiety precisely locates the interfaces through electrostatic interaction and simultaneously NBD entirely embeds into the waterless core via hydrophobic interaction. Thus, high-fidelity and background-free fluorescence imaging of LDs are expectably realized in living cells in situ. Moreover, LDs in turbid tissues like skeletal muscle slices have been clearly imaged (up to 82 μm depth) by a two-photon microscope. Importantly, using N-Cy, we not only intuitively monitored the variations of LDs in number, size, and morphology but also clearly revealed their abnormity in hepatic tissues resulting from fatty liver. Therefore, these unique probes provide excellent imaging tools for elucidating LD-related physiological and pathological processes and the interface-targeting strategy possesses universal significance for designing probes with ultrahigh selectivity.

中文翻译：

界面靶向策略使两光子荧光脂质液滴探针能够对混浊组织进行高保真成像并检测脂肪肝

具有独特界面结构的脂滴（LDs）不仅在保护细胞免受脂毒性和脂细胞凋亡方面起着至关重要的作用，而且还与许多疾病如脂肪肝和糖尿病密切相关。因此，作为重要的应用生物材料之一，对活细胞和组织中的LDs进行原位和高保真成像具有超高选择性的荧光探针对于阐明相关的生理和病理事件以及检测相关疾病至关重要。但是，仅利用LD的无水中性核而不考虑独特的磷脂单层界面的可用探针显示出低选择性。它们无法将LD的中性核心与细胞内其他亲脂性微环境区分开，从而导致广泛的云状背景噪声并严重限制了其生物应用。在此，为了设计具有超高选择性的LD探针，充分考虑了LD的特殊界面结构，因此首次提出了接口靶向策略。根据新策略，我们开发了两种两亲荧光探针（N-Cy和N-Py），是通过将不同的阳离子引入亲脂性荧光团（硝基苯并恶二唑（NBD））中来实现的。因此，它们的阳离子部分通过静电相互作用精确定位界面，同时NBD通过疏水相互作用完全嵌入无水核中。因此，期望在活细胞中原位实现LD的高保真和无背景荧光成像。此外，已经通过双光子显微镜清楚地成像了浑浊组织（如骨骼肌切片）中的LD（最大深度为82μm）。重要的是，使用N-Cy，我们不仅直观地监测了LD的数量，大小和形态的变化，而且还清楚地揭示了它们在脂肪肝引起的肝组织中的异常。因此，这些独特的探针为阐明LD相关的生理和病理过程提供了出色的成像工具，并且界面靶向策略对于设计具有超高选择性的探针具有普遍意义。

更新日期：2018-03-09

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