Ultra-pH-sensitive nanoprobe library with broad pH tunability and fluorescence emissions.
Ultra-pH-sensitive nanoprobe library with broad pH tunability and fluorescence emissions.
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DOI：
10.1021/ja5053158
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发表时间：
2014-08-06
影响因子：
15
通讯作者：
Gao, Jinming
中科院分区：
文献类型：
--
作者：
Ma, Xinpeng;Wang, Yiguang;Zhao, Tian;Li, Yang;Su, Lee-Chun;Wang, Zhaohui;Huang, Gang;Sumer, Baran D.;Gao, Jinming
pH是一个重要的生理参数，在细胞和组织的稳态中起着关键作用。传统的小分子pH传感器（例如，荧光素，Lysosensor）受到宽pH响应和受限荧光发射的限制。以前，我们报道了使用具有小斯托克斯位移（<40 nm）的荧光团开发具有尖锐pH响应的超pH敏感（UPS）纳米探针。在这项研究中，我们将UPS设计扩展到具有操作员预定的pH转换和宽荧光发射（400-820 nm）的纳米探针库。采用共聚物策略来微调可电离疏水嵌段的疏水性，这导致基于标准曲线的期望的过渡pH。有趣的是，匹配单体的疏水性对于实现急剧的pH转变至关重要。为了克服荧光团的限制，我们引入了与荧光猝灭剂（FQs）缀合的共聚物。在胶束状态下，荧光量子点有效地抑制了荧光团的发射，而不管它们的斯托克斯位移，并进一步增加荧光激活比。作为概念证明，我们生成了10个纳米探针的文库，每个探针编码有独特的荧光团。纳米探针覆盖pH（4-7.4）的整个生理范围，具有0.3 pH增量。每个纳米探针保持急剧的pH转变（开/关<0.25pH）和高荧光活化比（开和关状态之间>50倍）。UPS库提供了一个有用的工具包来研究许多病理生理学适应症中的pH调节（例如，癌症、溶酶体催化剂）以及建立用于癌症成像和药物递送的肿瘤可激活系统。
pH is an important physiological parameter that plays a critical role in cellular and tissue homeostasis. Conventional small molecular pH sensors (e.g., fluorescein, Lysosensor) are limited by broad pH response and restricted fluorescent emissions. Previously, we reported the development of ultra-pH-sensitive (UPS) nanoprobes with sharp pH response using fluorophores with small Stokes shifts (<40 nm). In this study, we expand the UPS design to a library of nanoprobes with operator-predetermined pH transitions and wide fluorescent emissions (400–820 nm). A copolymer strategy was employed to fine tune the hydrophobicity of the ionizable hydrophobic block, which led to a desired transition pH based on standard curves. Interestingly, matching the hydrophobicity of the monomers was critical to achieve a sharp pH transition. To overcome the fluorophore limitations, we introduced copolymers conjugated with fluorescence quenchers (FQs). In the micelle state, the FQs effectively suppressed the emission of fluorophores regardless of their Stokes shifts and further increased the fluorescence activation ratios. As a proof of concept, we generated a library of 10 nanoprobes each encoded with a unique fluorophore. The nanoprobes cover the entire physiologic range of pH (4–7.4) with 0.3 pH increments. Each nanoprobe maintained a sharp pH transition (on/off < 0.25 pH) and high fluorescence activation ratio (>50-fold between on and off states). The UPS library provides a useful toolkit to study pH regulation in many pathophysiological indications (e.g., cancer, lysosome catabolism) as well as establishing tumor-activatable systems for cancer imaging and drug delivery.
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影响因子：
10.8
作者：
Lee S;Ryu JH;Park K;Lee A;Lee SY;Youn IC;Ahn CH;Yoon SM;Myung SJ;Moon DH;Chen X;Choi K;Kwon IC;Kim K
通讯作者：
Kim K
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Li, Pilong;Banjade, Sudeep;Cheng, Hui-Chun;Kim, Soyeon;Chen, Baoyu;Guo, Liang;Llaguno, Marc;Hollingsworth, Javoris V.;King, David S.;Banani, Salman F.;Russo, Paul S.;Jiang, Qiu-Xing;Nixon, B. Tracy;Rosen, Michael K.
通讯作者：
Rosen, Michael K.
影响因子：
41.2
作者：
Bellomo, EG;Wyrsta, MD;Deming, TJ
通讯作者：
Deming, TJ
影响因子：
4.7
作者：
Maxwell, Dustin;Chang, Qing;Zhang, Xu;Barnett, Edward M.;Piwnica-Worms, David
通讯作者：
Piwnica-Worms, David