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Enzyme-instructed self-assembly leads to activation of optical properties for selective fluorescence detection and photodynamic ablation of cancer cells

Abstract

Fluorescence and photoactivity dual-activatable probes are particularly valuable for cancer theranostics as they allow for sensitive fluorescent diagnosis and on-demand photodynamic therapy (PDT) against targeted cancer cells at the same time, which undoubtedly promote the diagnostic accuracy and reduce the side effects on normal tissues/cells. Here, we show that enzyme-instructed self-assembly (EISA) is an ideal strategy to develop fluorescence and reactive oxygen species (ROS) generation capability dual-activatable probe with aggregation-induced emission (AIE) signature. As a proof-of-concept, we design and synthesize a precursor TPE-Py-FpYGpYGpY that consists of an AIE luminogen (TPE-Py) and a short peptide with three tyrosine phosphates (pY), which permits selective fluorescence visualization and PDT of alkaline phosphatase (ALP)-overexpressed cancer cells. TPE-Py-FpYGpYGpY has good aqueous solubility thanks to the hydrophilic phosphotyrosine residues and hence leads to weak fluorescence and negligible ROS generation ability. After ALP enzymatic dephosphorylation of the precursors, however, self-assembly of the ALP-catalysed products occurs and the resultant nanostructures are activated to be highly emissive and efficiently produce ROS. Cellular studies reveal that TPE-Py-FpYGpYGpY is capable of differentiating cancer cells and normal cells, specifically pinpointing and suppressing ALP-overexpressed cancer cells. This study may inspire new insights into the design of advanced activatable molecular probes.

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Publication details

The article was received on 10 Oct 2017, accepted on 14 Nov 2017 and first published on 14 Nov 2017


Article type: Paper
DOI: 10.1039/C7TB02685D
Citation: J. Mater. Chem. B, 2017, Accepted Manuscript
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    Enzyme-instructed self-assembly leads to activation of optical properties for selective fluorescence detection and photodynamic ablation of cancer cells

    S. Ji, H. Gao, W. Mu, X. Ni, X. Yi, J. Shen, Q. Liu, P. Bao and D. Ding, J. Mater. Chem. B, 2017, Accepted Manuscript , DOI: 10.1039/C7TB02685D

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