TY - JOUR
T1 - Selective tracking of lysosomal cu2+ ions using simultaneous target- and location-activated fluorescent nanoprobes
AU - Li, Yinhui
AU - Zhao, Yirong
AU - Chan, Winghong
AU - Wang, Yijun
AU - You, Qihua
AU - Liu, Changhui
AU - Zheng, Jing
AU - Li, Jishan
AU - Yang, Sheng
AU - Yang, Ronghua
N1 - Funding information:
The authors acknowledge financial support through the National Natural Science Foundation of China (Nos. 21305036, 21135001, and J1103312), the Foundation for Innovative Research Groups of NSFC (No. 21221003), the “973” National Key Basic Research Program (No. 2011CB91100-0), Hunan Provincial Natural Science Foundation of China (No. 2015JJ3035), and the Fundamental Research Funds for the Central Universities.
Publisher copyright:
© 2014 American Chemical Society
PY - 2015/1/6
Y1 - 2015/1/6
N2 - 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 rhodamine-spiropyran 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 β-cyclodextrin (β-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 αvβ3 and αvβ5 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.
AB - 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 rhodamine-spiropyran 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 β-cyclodextrin (β-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 αvβ3 and αvβ5 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.
UR - http://www.scopus.com/inward/record.url?scp=84920497852&partnerID=8YFLogxK
U2 - 10.1021/ac503240x
DO - 10.1021/ac503240x
M3 - Journal article
C2 - 25435382
AN - SCOPUS:84920497852
SN - 0003-2700
VL - 87
SP - 584
EP - 591
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 1
ER -
