Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

Selective tracking of lysosomal Cu2+ ions using simultaneous target- and location-activated fluorescent nanoprobes

Language

English

Abstract

© 2014 American Chemical Society. 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.

Publication Date

2015

Source Publication Title

Analytical Chemistry

Volume

87

Issue

1

Start Page

584

End Page

591

Publisher

American Chemical Society

DOI

10.1021/ac503240x

Link to Publisher's Edition

http://dx.doi.org/10.1021/ac503240x

ISSN (print)

00032700

ISSN (electronic)

15206882

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