Search

A two-photon (TP) fluorescence probe has been developed for imaging endogenous FA fluxes during metabolic and epigenetic processes in animal models, especially in live brains. [ABSTRACT FROM AUTHOR]

Imbalanced iron homeostasis plays a crucial role in neurological diseases, yet direct imaging evidence revealing the distribution of active ferrous iron (Fe2+) in the living brain remains scarce. Here, we present a near-infrared excited two-photon fluorescent probe (FeP) for imaging changes of Fe2+ flux in the living epileptic mouse brain. In vivo 3D two-photon brain imaging with FeP directly revealed abnormal elevation of Fe2+ in the epileptic mouse brain. Moreover, we found that dihydroartemisinin (DHA), a lead compound discovered through probe-based high-throughput screening, plays a critical role in modulating iron homeostasis. In addition, we revealed that DHA might exert its antiepileptic effects by modulating iron homeostasis in the brain and finally inhibiting ferroptosis. This work provides a reliable chemical tool for assessing the status of ferrous iron in the living epileptic mouse brain and may aid the rapid discovery of antiepileptic drug candidates. [Display omitted] • FeP, a fluorescent probe, is suitable for brain imaging ferrous iron flux in vivo • 3D two-photon imaging reveals elevation of ferrous iron in the epileptic mouse brain • Dihydroartemisinin (DHA) can modulate iron homeostasis in the epileptic mouse • DHA exhibits a potential antiepileptic effect in the epileptic mouse model Shao et al. develop a near-infrared excited two-photon fluorescent probe for imaging ferrous iron (Fe2+) in brain. Using in vivo 3D two-photon imaging, they observe abnormal elevation of Fe2+ in the epileptic mouse brain and demonstrate that dihydroartemisinin exhibits antiepileptic effects by modulating iron homeostasis in the mouse brain. [ABSTRACT FROM AUTHOR]

Achieving selective release of chemical anticancer agents and improving therapeutic efficacy has always been a hot spot in the field of cancer research, yet how to achieve this remains a great challenge. In this work, we constructed a novel chemical anticancer agent (named MCLOP) by introducing naphthalimide into the skeleton of methylene blue (MB). Under the stimulation by cellular hypochlorous acid (HClO) and visible light, selective release of active naphthalimide can be achieved within breast cancer cell lines, the release process of which can be tracked visually using near-infrared fluorescence of MB (685 nm). More importantly, we developed biotinylated curcumin (Cur-Bio) as a new chemosensitizer, which significantly enhanced the ability of MCLOP to induce autophagic cell death of breast cancer cells. This synergistic treatment strategy exhibited an excellent anti-proliferation effect on breast cancer cells in vitro , three-dimensional (3D) cell sphere model, and mouse tumor model in vivo. This work provides a new strategy for the treatment of breast cancer and also opens new opportunities for the efficient treatment of cancer with curcumin-based chemosensitizer. [Display omitted] • New anticancer agent MCLOP was developed based on naphthalimide and methylene blue. • Stimulation with HClO and visible light release active naphthalimide in MCF-7 cells. • The biotinylated curcumin (Cur-Bio) was constructed as a new chemosensitizer. • Cur-Bio enhances the ability of MCLOP to induce autophagic cell death of MCF-7 cells. • Treatment with MCLOP and Cur-Bio exhibits a synergistic anticancer effect in vivo. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurodegenerative disease, and accumulating evidence suggests its pathological progression is closely associated with peroxynitrite (ONOO−). However, understanding the function remains challenging due to a lack of in vivo imaging probes for ONOO− determination in epileptic brains. Here, the first near‐infrared imaging probe (named ONP) is presented for tracking endogenous ONOO− in brains of kainate‐induced epileptic seizures with high sensitivity and selectivity. Using this probe, the dynamic changes of endogenous ONOO− fluxes in epileptic brains are effectively monitored with excellent temporal and spatial resolution. In vivo visualization and in situ imaging of hippocampal regions clearly reveal that a higher concentration of ONOO− in the epileptic brains associates with severe neuronal damage and epileptogenesis; curcumin administration can eliminate excessively increased ONOO−, further effectively protecting neuronal cells. Moreover, by combining high‐content analysis and ONP, a high‐throughput screening method for antiepileptic inhibitors is constructed, which provides a rapid imaging/screening approach for understanding epilepsy pathology and accelerating antiseizure therapeutic discovery. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common malignant tumor worldwide. The problem of drug resistance in lung cancer leads to treatment failure and recurrence in more than 90% of cancer patients. Thus, developing chemical probes that can observe drug-resistant lung cancer cells in real-time and eliminate them is of great interest. However, such tools that can simultaneously probe drug-resistant lung cancer cells and therapeutic modes of action have not yet been developed. In this work, we reported a fluorescent prodrug that can be activated in cancer cell lysosomes to release amonafide (ANF) and aniline mustard, where the fluorescent signal of ANF (λ ex /λ em = 405/570 −620 nm) can be tracked by super-resolution imaging in live cancer cells. With imaging studies, we found that this new fluorescent prodrug uniquely displays an autophagy-driven ferroptosis-inducing effect, accompanied by the accumulation of intracellular ferrous ions and lipid peroxidation. More importantly, the fluorescent prodrug exhibits potential anti-proliferative activity, especially against drug-resistant A549R lung cancer cells (IC 50 , ∼ 3 μM), better than the positive control drug cisplatin (IC 50 , ∼ 27 μM). This work indicates that the development of fluorescent prodrugs as autophagy-driven ferroptosis inducers may represent a viable approach for targeting drug-resistant cancer cells. [Display omitted] • A new fluorescent prodrug for fighting drug-resistant lung cancer cells was developed. • This fluorescent prodrug can be activated in cancer cell lysosomes to release ANF. • The fluorescent signal of ANF can be tracked by super-resolution imaging in live cells. • This new fluorescent prodrug displays an autophagy-driven ferroptosis-inducing effect. [ABSTRACT FROM AUTHOR]

[Display omitted] • UMIGH NPs, a targeted nanoplatform with multifunction and cascade effect, was introduced to treat colon cancer in mice. • UMIGH NPs could reduce the impact of HSPs at an upstream node through decreasing the adenosine triphosphate with glucose oxidase effectively. • UMIGH NPs realized the synergistic starvation therapy/low-temperature PTT with improved anti-tumor performance. Hypothermal photothermal therapy, as a non-invasive therapy method, is becoming ever more prevalent. However, due to cellular heat resistance from the generation of heat shock proteins (HSPs) and the monotonicity of therapeutic modality, the antitumor efficacy is severely restricted. Herein, a self-supplied O 2 multifunctional nanoplatform mediated by glucose oxidase (GOx) is developed, which may combine starvation therapy (ST) and hypothermal photothermal therapy (HPTT) for tumor therapy. The obtained nanoplatform, UM@ICG@GOX@HA (UMIGH), was assembled by the UIO-66 core, MnO 2 , indocyanine green (ICG) and hyaluronic acid (HA). GOx was introduced to decrease the ATP level thus alleviating the HSPs-mediated heat tolerance, while the loaded MnO 2 could decompose intratumoral H 2 O 2 into O 2 , which enhanced the effect of HPTT and ST. Due to the coated HA, UMIGH could target the high expressed CD44 in CT26 tumor cells. The active targeting and NPs-associated passive targeting promoted the uptake of nanoparticles. Furthermore, ICG encapsulated in UMIGH NPs could also accurately image tumors. This synergistic treatment strategy of HPTT and ST exhibited an excellent anti-proliferation effect on colon cancer cells in vitro and mouse xenograft model in vivo , which might bring an informatic strategy for future investigations. [ABSTRACT FROM AUTHOR]

Hydrogen polysulfide (H 2 S n , n > 1), a member of reactive sulfur species (RSS), is primarily generated during the crosstalk between H 2 S and reactive oxygen species (ROS), which plays important role in physiological and pathological processes. Ferroptosis is a new non-classical mode of cell death, in which ROS-associated lipid peroxidation and iron-dependent accumulation are the main features. However, the biological effects of H 2 S n on ferroptosis and the detailed mechanisms of action remain poorly understood. Thus, there is an urgent need to develop highly selective and sensitive chemical tools for monitoring H 2 S n in living cells. Herein, we develop a two-photon fluorescent probe (PSP) for specifically imaging H 2 S n in live cells and tumor spheroids. This probe exhibited a sensitive and selective response to H 2 S n , which had been used for imaging exogenous and endogenous H 2 S n in living cells by confocal imaging and high content imaging. PSP exhibits excellent photo-stability and two-photon imaging performance when irradiating at 880 nm in 3D HeLa multicellular tumor spheroids. Importantly, our studies revealed that H 2 S n levels were significantly up-regulated during ferroptosis. These excellent properties ensure that PSP is a promising two-photon probe for exploring the biological and pathological effects of H 2 S n during ferroptosis. [Display omitted] • A two-photon fluorescent probe, PSP, was developed for monitoring of H 2 S n. • PSP exhibited high specificity and sensitivity to H 2 S n. • PSP can be used to detect the up-regulation of H 2 S n during ferroptosis in living cells. • PSP can be applied for imaging of endogenous H 2 S n in HeLa MCTSs. [ABSTRACT FROM AUTHOR]