“Dual-Key-and-Lock” Ruthenium Complex Probe for Lysosomal Formaldehyde in Cancer Cells and Tumors

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) centre 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 favourable 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 "dualkey-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.

A highly X-ray sensitive iridium prodrug for visualized tumor radiochemotherapy

“…The major part is the six coordinated Ir(III) part, which is both a good chemotherapeutic drug and radiotherapy drug, and at the same time, it has strong luminescence emission. In order to accurately visualize the location of tumor sites, the prodrug Ir-NB is designed to include another two parts: one is a nitrobenzoyl motif, a strong electron acceptor, which can be used to quench the luminescence emission of the Ir(III) complex owing to the photoinduced electron transfer (PET) process; 18,27 the other one is an acidity-sensitive imine bond, which can be used as a pH responsive linker to be broken in the TME to reproduce the luminescence emission of the Ir(III) complex (Fig. 1c).…”

The Beast of Beauty: Environmental and Health Concerns of Toxic Components in Cosmetics

“…However, research has revealed that the nasal route or inhalation is the most common and prominent route of FA exposure, because most indoor contaminants have been found in gaseous form in the air [99]. The continuous and delayed exposure with FA is associated with a broad range of serious health concerns such as various types of cancers including cutaneous carcinoma and sinus carcinoma, causes allergy, and also produces a mutagenic effect [100]. Moreover, long-term exposure with a high intensity of FA led to increasing the risk of myeloid leukemia progression [101].…”

Development of “dual-key-and-lock” responsive probes for biosensing and imaging

“…1B). 38 The reaction between formaldehyde and Ru-FA occurs at pH < 6.0, resulting in cleavage of 2,4-dinitrobenzene (DNB) electron acceptor to form Ru-NR and thus turn "ON" luminescence (DoL: 19.8 nM). Different with the morpholine-guided lysosome targeting, this "dual-key-and-lock" probe precludes false positive signals derived from the probe being triggered "ON" in other organelles and then accumulated in lysosome.…”