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Indexed by:期刊论文

Date of Publication:2019-05-29

Journal:JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Included Journals:EI、PubMed、SCIE

Volume:141

Issue:21

Page Number:8462-8472

ISSN No.:0002-7863

Key Words:Biocompatibility; Cells; Cytology; Diagnosis; Diseases; Formaldehyde; Keys (for locks); Locks (fasteners); Luminescence; Mammals; Probes; Tumors, Acidic microenvironment; Biomedical investigations; Electron withdrawing group; Formaldehyde detection; Luminescence imaging; Ruthenium complexes; Spectrometric analysis; Treatment monitoring, Ruthenium compounds

Abstract:Biomedical investigations reveal that excessive formaldehyde generation is possibly a critical factor for tissue cancerization, cancer progression, and metastasis. Responsive molecular probes that can detect lysosomal formaldehyde in live cells and tumors and monitor drug-triggered formaldehyde scavenging contribute potentially to future cancer diagnosis and treatment monitoring. Herein, a novel "dual-key-and-lock" strategy-based ruthenium(II) complex probe, Ru-FA, is reported as an effective tool for formaldehyde detection in vitro and in vivo. Ru-FA shows weak luminescence due to photon-induced electron transfer (PET) process from Ru(II) center to electron withdrawing group 2,4-dinitrobenzene (DNB). Triggered by the specific reaction with formaldehyde (first "key") in an acidic microenvironment (second "key"), DNB is cleaved from Ru-FA, affording an emissive Ru(II) complex derivative, Ru-NR. Spectrometric analysis including steady-state and time-gated luminescence indicates that Ru-FA is favorable to be used as the probe for quantification of formaldehyde in human sera and mouse organs. Ru-FA is biocompatible and cell membrane permeable. Together with its smart "dual-key-and-lock" response to formaldehyde, luminescence imaging of lysosomal formaldehyde in live cells, visualization of tumor-derived endogenous formaldehyde, and monitoring of formaldehyde scavenging in mice were achieved, followed by the successful demonstration on detection of formaldehyde in tumors and other organs. These in vivo and in vitro detection confirm not only the excessive formaldehyde generation in tumors, but also the efficient drug administration to scavenge formaldehyde, demonstrating the potential application of Ru-FA in cancer diagnosis and treatment monitoring through lysosomal formaldehyde detection.