期刊
ANALYTICAL CHEMISTRY
卷 87, 期 1, 页码 584-591出版社
AMER CHEMICAL SOC
DOI: 10.1021/ac503240x
关键词
-
资金
- National Natural Science Foundation of China [21305036, 21135001, J1103312]
- Foundation for Innovative Research Groups of NSFC [21221003]
- 973 National Key Basic Research Program [2011CB91100-0]
- Hunan Provincial Natural Science Foundation of China [2015JJ3035]
- Fundamental Research Funds for the Central Universities
Levels of lysosomal copper are tightly regulated in the human body. However, few methods for monitoring dynamic changes in copper pools are available, thus limiting the ability to diagnostically assess the influence of copper accumulation on health status. We herein report the development of a dual target and location-activated rhodaminespiropyran probe, termed Rhod-SP, activated by the presence of lysosomal Cu2+. Rhod-SP contains a proton recognition unit of spiropyran, which provides molecular switching capability, and a latent rhodamine fluorophore for signal transduction. Upon activation by lysosomal acidic pH, Rhod-SP binds with Cu2+ by spiropyran-based proton activation, promoting, in turn, rhodamine ring opening, which shows a switched on fluorescence signal. However, to protect Rhod-SP from degradation and interference by the physiological environment, it is engineered on mesoporous silica nanoparticles (MSNs), and the surface of Rhod-SP@MSNs is further anchored with beta-cyclodextrin (beta-CD) to enhance the solubility and bioavailability of Rhod-SP@MSN-CD. Next, to enhance cell specificity, a guiding unit of c(RGDyK) peptide conjugated adamantane (Ad-RGD) as prototypical system, is incorporated on the surface of Rhod-SP@MSN-CD to target integrin alpha(v)beta(3) and alpha(v)beta(5) overexpressed on cancer cells. Fluorescence imaging showed that both Rhod-SP@MSN-CD and Rhod-SP@MSN-CD-RGD were suitable for visualizing exogenous and endogenous Cu2+ in lysosomes of living cells. This strategy addresses some common challenges of chemical probes in biosensing, such as spatial resolution in cell imaging, the solubility and stability in biological system, and the interference from intracellular species. The newly designed nanoprobe, which allows one to track, on a location-specific basis, and visualize lysosomal Cu2+, offers a potentially rich opportunity to examine copper physiology in both healthy and diseased states.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据