Investigation of endosome and lysosome biology by ultra pH-sensitive nanoprobes.
Investigation of endosome and lysosome biology by ultra pH-sensitive nanoprobes.
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DOI：
10.1016/j.addr.2016.08.014
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发表时间：
2017-04
影响因子：
16.1
通讯作者：
Gao J
中科院分区：
文献类型：
--
作者：
Wang C;Zhao T;Li Y;Huang G;White MA;Gao J
内体和溶酶体在细胞生理学的各个方面发挥着关键作用，例如营养传感、受体回收、蛋白质/脂质分解代谢和细胞死亡。在药物递送中，纳米载体治疗有效负载的内体释放对于实现药物有效递送以到达细胞内靶标也很重要。最近，我们发明了一个超 pH 敏感 (UPS) 纳米探针库，对细微的 pH 变化具有精致的荧光响应。 UPS 纳米探针还对具有广泛 pH 响应的小分子碱（例如氯喹和 NH4Cl）表现出强烈的 pH 特异性缓冲效应。 UPS 纳米探针从 7.4 到 4.0 的可调 pH 值转换覆盖了内吞细胞器（例如早期和晚期内体）和溶酶体的整个生理 pH 值。 UPS 纳米探针的这些独特的物理化学特性允许采用“检测和扰动”策略来研究细胞信号传导和代谢中的管腔 pH 值，从而为内体和溶酶体的生物学研究引入了纳米技术支持的范例。
Endosomes and lysosomes play a critical role in various aspects of cell physiology such as nutrient sensing, receptor recycling, protein/lipid catabolism, and cell death. In drug delivery, endosomal release of therapeutic payloads from nanocarriers is also important in achieving efficient delivery of drugs to reach their intracellular targets. Recently, we invented a library of ultra pH-sensitive (UPS) nanoprobes with exquisite fluorescence response to subtle pH changes. The UPS nanoprobes also displayed strong pH-specific buffer effect over small molecular bases with broad pH responses (e.g., chloroquine and NH4Cl). Tunable pH transitions from 7.4 to 4.0 of UPS nanoprobes cover the entire physiological pH of endocytic organelles (e.g., early and late endosomes) and lysosomes. These unique physico-chemical properties of UPS nanoprobes allowed a ‘detect and perturbation’ strategy for the investigation of luminal pH in cell signaling and metabolism, which introduces a nanotechnology-enabled paradigm for the biological studies of endosomes and lysosomes.