Different Valence States of Copper Ion Delivery against Triple-Negative Breast Cancer.

Different valence states of copper (Cu) ions are involved in complicated redox reactions in vivo, which are closely related to tumor proliferation and death pathways, such as cuproptosis and chemodynamic therapy (CDT). Cu ion mediated Fenton-like reagents induced tumor cell death which presents compelling attention for the CDT of tumors. However, the superiority of different valence states of Cu ions in the antitumor effect is unknown. In this study, we investigated different valence states of Cu ions in modulating tumor cell death by Cu-chelated cyanine dye against triple-negative breast cancer. The cuprous ion (Cu+) and copper ion (Cu2+) were chelated with four nitrogen atoms of dipicolylethylenediamine-modified cyanine for the construction of Cu+ and Cu2+ chelated cyanine dyes (denoted as CC1 and CC2, respectively). Upon 660 nm laser irradiation, the CC1 or CC2 can generate reactive oxygen species, which could disrupt the cyanine structure, achieving the rapid release of Cu ions and initiating the Fenton-like reaction for CDT. Compared with Cu2+-based Fenton-like reagent, the CC1 with Cu+ exhibited a better therapeutic outcome for the tumor due to there being no need for a reduction by glutathione and a shorter route to generate more hydroxyl radicals. Our findings suggest the precision delivery of Cu+ could achieve highly efficient antitumor therapy.

Synchronous Interventions of Glucose and Mitochondrial Metabolisms for Antitumor Bioenergetic Therapy.

Hydrogen sulfide (H2 S)-based mitochondrial bioenergetic intervention is an attractive therapeutic modality. However, its therapeutic efficacy is limited owing to metabolic plasticity, which allows tumors to shift their metabolic phenotype between oxidative phosphorylation and glycolysis for energy compensation. To overcome this flexibility, a glycopolymer containing a caged H2 S and hydrogen peroxide (H2 O2 ) dual-donor (1-thio-ß-D-glucose [thioglucose]) is synthesized to wrap glucose oxidase (GOx) for complete depletion of tumorigenic energy sources. The loaded GOx catalyzes the glutathione-activated thioglucose to generate cytotoxic H2 S/H2 O2 , which further induces synergistic defects in mitochondrial function by suppressing cytochrome c oxidase expression and damaging the mitochondrial membrane potential. GOx also blocks glycolysis by depleting endogenous glucose. This synchronous intervention strategy exhibits good anticancer performance, broadening the horizon of antitumor bioenergetic therapy.

A FRET-Based Ratiometric H2S Sensor for Sensitive Optical Molecular Imaging in Second Near-Infrared Window.

Second near-infrared (NIR-II) window optical molecular imaging kicks off a new revolution in high-quality imaging in vivo, but always suffers from the hurdles of inevitable tissue autofluorescence background and NIR-II probe development. Here, we prepare a Förster resonance energy transfer-based ratiometric NIR-II window hydrogen sulfide (H2S) sensor through the combination of an H2S-responsive NIR-II cyanine dye (acceptor, LET-1055) and an H2S-inert rhodamine hybrid polymethine dye (donor, Rh930). This sensor not only exhibits high sensitivity and selectivity, but also shows rapid reaction kinetics (~20 min) and relatively low limit of detection (~96 nM) toward H2S, allowing in vivo ratiometric NIR-II fluorescence imaging of orthotopic liver and colon tumors and visualization of the drug-induced hepatic H2S fluctuations. Our findings provide the potential for advancing the feasibility of NIR-II activity-based sensing for in vivo clinical diagnosis.

Activatable NIR-II Fluorescence Probe for Highly Sensitive and Selective Visualization of Glutathione In Vivo.

Visualization of glutathione (GSH) enables us to understand GSH-related pathophysiological processes in living subjects. Currently, in vivo visualization methods of GSH are based on visible or first near-infrared (NIR-I) window fluorescence (FL) probes, which possess limitations due to their low tissue penetration depth and strong tissue autofluorescence. Herein, we developed a GSH-activatable second near-infrared (NIR-II) window FL probe (denoted as LET-7) for highly sensitive and selective visualization of GSH in vivo. LET-7, composed of an anionic polymethylcyanide skeleton linked with a FL quenching group of 3,5-bis(trifluoromethyl)benzenethiol, can be specifically activated by GSH, thus triggering a significant NIR-II FL emission enhancement with excellent photostability, which enables us to efficiently distinguish GSH from closely related low-molecular-weight biothiols. The limit of detection of LET-7 for GSH was determined to be as low as 85 nM. Most intriguingly, the in vivo studies demonstrated that LET-7 showed high sensitivity and good selectivity toward GSH. Therefore, our study provides a solution to design activatable NIR-II FL probes for in vivo imaging of GSH and other disease-related biomarkers.

Discoveries of the specific expression of lncRNAs and mRNAs in hippocampus of rats after traumatic brain injury.

Objects: Explore the relationship between the neural function deficit and the changes of lncRNA and mRNA in hippocampus after traumatic brain injury (TBI) in rats. Methods: Twenty male rats weighted 200-240 grams were randomly divided into sham group and TBI group. Neurologic severity score (NSS) was performed after operation, and the hippocampus of rats was collected for long non-coding RNAs (lncRNAs), mRNAs microarray detection, real-time quantitative PCR Detecting System (Q-PCR), western blot (WB) detection, and serum biochemical detection. Results: The NSS score of the TBI group was significantly higher than the sham group. Compared with the sham group, 270 lncRNAs changed in the TBI group, of which 224 were up-regulated and 46 were down-regulated. Among up-regulated lncRNAs, mRNAs were distributed in upstream of 22 lncRNAs, downstream of 17 lncRNAs, overlapping regions of 48 lncRNAs, and antisense chains of 21 lncRNAs. Among down-regulated lncRNAs, mRNAs were distributed in upstream of 6 lncRNAs, downstream of 3 lncRNAs, overlapping regions of 10 lncRNAs, and antisense chains of 8 lncRNAs. Compared with the sham group, 1054 mRNA changed in the TBI group, of which 921 mRNA were up-regulated and 133 mRNA were down-regulated. The expression changes of ENSRNOT000063054, ENSRNOT000052790, ENSRNOT00000054410, ENSRNOT000063242, and ENSRNOT000069411 IncRNA regulate the expression of Top2a, RT1-CE11, Papss2, Stk32a, and Grid2 gene. Conclusion: The present study detected the differential expression of lncRNAs and mRNAs in hippocampi of rats subjected to TBI, and discussed their relation, primarily.