In Vivo Targeting of Hydrogen Peroxide by Activatable Cell-Penetrating Peptides

Abstract

A hydrogen peroxide (H2O2)-activated cell-penetrating peptide was developed through incorporation of a boronic acid-containing cleavable linker between polycationic cell-penetrating peptide and polyanionic fragments. Fluorescence labeling of the two ends of the molecule enabled monitoring its reaction with H2O2 through release of the highly adhesive cell-penetrating peptide and disruption of fluorescence resonance energy transfer. The H2O2 sensor selectively reacts with endogenous H2O2 in cell culture to monitor the oxidative burst of promyelocytes and in vivo to image lung inflammation. Targeting H2O2 has potential applications in imaging and therapy of diseases related to oxidative stress.

Highly selective and sensitive surface enhanced Raman scattering nanosensors for detection of hydrogen peroxide in living cells

“…5C,D), due to that the H 2 O 2 concentration in HeLa cells is higher than that in HL-7702 cells. Using the I 1600 /I 1131 ratio change from the exogenous H 2 O 2 application experiment as a calibration curve, we calculated that under the aforementioned conditions, PMA stimulated HeLa cells and HL-7702 cells generate H 2 O 2 at a rate of 1.08 nmol/10 4 cells/h and 0.85 nmol/10 4 cells/h, which is in agreement with previously reported measurements (Weinstain et al, 2014), indicating Au NPs/4-CA could be used as nanosensors for qualitative and quantitative detection of H 2 O 2 in living cells.…”

“…Recent researches show that arylboronates could be oxidized by H 2 O 2 selectively to provide phenols under mild conditions (Weinstain et al, 2014;Sun et al, 2013;Miller et al, 2005). Based on this reaction, we fabricated SERS nanosensors by modifying Au NPs with 4-CA (Au NPs/4-CA) for the real-time determination of H 2 O 2 in living cells (Scheme 1).…”

De novo acetate production is coupled to central carbon metabolism in mammals

“…ROS levels are dynamic and at steady state, intracellular concentrations of H 2 O 2 vary from nM to µM 38,39 , while extracellular concentrations of H 2 O 2 may be 10 to 100 times higher under certain circumstances, such as inflammation 40 . Consistent with this pathway, cancer cells have been shown to produce H 2 O 2 at a rate of around 1 nmol/10 4 cells/hour 41,42 , while the combined pyruvate generation and secretion rate (Fig. 1b) was found to be around 2 nmol/10 4 cells/hour.…”

Assessment of the in vitro anti-lipid peroxidative activity of Costus afer stem extract

“…Among the important ROS is hydrogen peroxide which is kept in check by the activities of catalase. Overproduction of hydrogen peroxide or probably if catalase activity is impaired, lesions like hyperpolarization of cell membranes [13], cell damage could occur which are implicated in a number of diseases such as diabetes, neurodegenerative, cardiovascular disorders, cancer, and aging [14]. Hydrogen peroxide reacts with partially reduced transition metal to generate the hydroxyl radical which is considered to be the most potent among the biologically active ROS [15,16].…”