Protective effects of cynaroside on oxidative stress in retinal pigment epithelial cells.

Cynaroside is a flavonoid compound proved to possess antioxidant activity, but its protective effect on age-related macular degeneration still remains unclear. In this study, the protective effects of cynaroside on oxidative stress and apoptosis in retinal pigment epithelial (RPE) cells induced by hydrogen peroxide (H2 O2 ) were investigated. Results showed that cynaroside effectively attenuated the decrease of cell activity induced by H2 O2 . The total reactive oxygen species can be remitted by decreasing malondialdehyde level, as well as increasing glutathione level, and superoxide dismutase and catalase activities. In addition, Western blot analysis indicated that cynaroside protected ARPE-19 cells from apoptosis through downregulation of caspase-3 protein activation which was controlled by the upstream proteins Bcl-2 and Bax. It was finally proved that cynaroside could enhance the antioxidant and antiapoptotic ability in ARPE-19 cells by promoting the expression of p-Akt.

A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent.

PURPOSE: Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent. METHODS: In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe3O4@OA NPs. The stability and anti phagocytosis of Fe3O4@OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo. RESULTS: These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe3O4@OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe3O4@OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose. CONCLUSIONS: The DG can validly enhance the tumor-targetting effect of Fe3O4@OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

A Near-Infrared Fluorescent Dye with Tunable Emission Wavelength and Stokes Shift as a High-Sensitivity Cysteine Nanoprobe for Monitoring Ischemic Stroke.

Sulfur-substituted dicyanomethylene-4H-chromene (DCM) derivatives based on the intramolecular charge transfer (ICT) mechanism were designed as near-infrared (NIR) fluorescent dyes. Using the Knoevenagel condensation method, the S-DCM-OH(835) fluorescence dye was synthesized, which had an emission wavelength exceeding 800 nm and 220 nm of a Stokes shift. Compared to commercial ICG, S-DCM-OH(835) was not only synchronized in emission wavelength but also far superior in Stokes shifts. These advantages made the design of S-DCM-NIR(835) based on this dye potentially valuable for biological applications. Based on this chemical structure, a fluorescent S-DCM-NIR(835) nanoprobe with a mean diameter of 17.69 nm was fabricated as the NIR imaging nanoprobe. Results showed that the nanoprobe maintained the high-specificity identification of cysteine (Cys) via the Michael addition reaction, with the detection limitation of 0.11 µM endogenous Cys. More importantly, in an ischemic stroke mouse model, the S-DCM-NIR(835) nanoprobe could monitor the Cys concentration change at stroke lesion due to the disruption of Cys metabolism under the ischemic stroke condition. Such a S-DCM-NIR(835) nanoprobe could not only differentiate the severity of the ischemic stroke using response time but also quantify the concentration of Cys in real-time in vivo.

Transmissible H-aggregated NIR-II fluorophore to the tumor cell membrane for enhanced PTT and synergistic therapy of cancer.

Photothermal therapy (PTT) combined with second near-infrared (NIR-II) fluorescence imaging (FI) has received increasing attention owing to its capacity for precise diagnosis and real-time monitoring of the therapeutic effects. It is of great clinical value to study organic small molecular fluorophores with both PTT and NIR-II FI functions. In this work, we report a skillfully fluorescent lipid nanosystem, the RR9 (RGDRRRRRRRRRC) peptide-coated anionic liposome loaded with organic NIR-II fluorophore IR-1061 and chemotherapeutic drug carboplatin, which is named RRIALP-C4. According to the structural interaction between IR-1061 and phospholipid bilayer demonstrated by molecular dynamics simulations, IR-1061 is rationally designed to possess the H-aggregated state versus the free state, thus rendering RRIALP-C4 with the activated dual-channel integrated function of intravital NIR-II FI and NIR-I PTT. Functionalization of RRIALP-C4 with RR9 peptide endows the specifically targeting capacity for αvß3-overexpressed tumor cells and, more importantly, allows IR-1061 to transfer the H-aggregated state from liposomes to the tumor cell membrane through enhanced membrane fusion, thereby maintaining its PTT effect in tumor tissues. In vivo experiments demonstrate that RRIALP-C4 can effectively visualize tumor tissues and systemic blood vessels with a high sign-to-background ratio (SBR) to realize the synergistic treatment of thermochemotherapy by PTT synergistically with temperature-sensitive drug release. Therefore, the strategy of enhanced PTT through H-aggregation of NIR-II fluorophore in the tumor cell membrane has great potential for developing lipid nanosystems with integrated diagnosis and treatment function.

D-A Type NIR-II Organic Molecules: Strategies for the Enhancement Fluorescence Brightness and Applications in NIR-II Fluorescence Imaging-Navigated Photothermal Therapy.

NIR-II fluorescence imaging (NIR-II FI) and photothermal therapy (PTT) have received broad attentions in precise tumor diagnosis and effective treatment attributed to high-resolution and deep tissue imaging, negligible invasivity, and high-efficiency treatment. Although many fluorescent molecules have been designed and conducted for NIR-II FI and PTT, it is still an enormous challenge for researchers to pioneer some rational design guidelines to improve fluorescence brightness. Organic D-A-type molecules, including small molecules and conjugated polymers, can be designed and developed to improve fluorescence brightness due to their tunable and easy functionalized chemical structures, allowing molecules tailored photophysical properties. In this review, some approaches to the development and design strategies of D-A type small molecules and conjugated polymers for the enhancement of fluorescence brightness are systemically introduced. Meanwhile, some applications of PTT and PTT-based combination therapy (such as PDT, chemotherapy, or gas therapy) assisted by NIR-II FI-based single or multiimaging technologies are classified and represented in detail as well. Finally, the current issues and challenges of NIR-II organic molecules in NIR-II FI-navigated PTT are summarized and discussed, which gives some guidelines for the future development direction of NIR-II organic molecules for NIR-II FI-navigated PTT.

Thiadiazoloquinoxaline derivative-based NIR-II organic molecules for NIR-II fluorescence imaging and photothermal therapy.

NIR-II FI has emerged as a promising imaging tool for in vivo precise diagnosis and visualization towards various diseases, ascribed to its merits of attenuated light scattering and tissue absorption and ignorable auto-fluorescence. Owing to its superiority in high specificity, low toxicity, and ignorable invasiveness, photothermal therapy (PTT) has developed as one of the most potential treatment methods for cancer treatment. Although organic optical agents with a donor-acceptor-donor (D-A-D) skeleton have been extensively applied to NIR-II FI and PTT, most were based on the three weak electron acceptors benzobisthiadiazole (BBTD), diketopyrrolopyrrole (DPP), and thiadiazoloquinoxaline (TTQ). Although the acceptor TTQ has developed as a promising acceptor to synthesize molecules for high-resolution NIR-II FI and PTT, reviews focused on TTQ based NIR-II organic molecules for NIR-II FI and PTT were still rarely reported. Hence, this review systemically summarized the current advanced process of TTQ based D-A-D type organic molecules for NIR-II FI and PTT. Firstly, some examples for NIR-II FI of tissue and immune and thrombosis NIR-II FI were presented in detail. Some examples of NIR-II FI-navigated PTT or combination therapy were discussed. Finally, some pending challenges in applying them to NIR-II FI and PTT are discussed.

Recent Advances of Organic Near-Infrared II Fluorophores in Optical Properties and Imaging Functions.

Near-infrared (NIR) fluorescence imaging (FI) has become a research hotspot because of its distinctive imaging properties: high temporal resolution and sensitivity. Especially in recent years, with the research focus of NIR FI shifting to the NIR-II region, which has better imaging performance, it is expected that NIR FI will find significant applications in the field of in vivo imaging. One of the most crucial directions for research into NIR-II FI is the promotion of novel NIR-II fluorophores with superior imaging properties. The remarkable advantages of organic NIR-II fluorophores in biosafety make them more promising than other fluorescent materials in certain applications. But serious defects in their fluorescence performance preclude particular imaging effects and limit imaging functions. In this review, we summarize and discuss the recent leading literature on overcoming the defects of organic NIR-II fluorophores, demonstrating the potential for further improving their imaging properties. In addition, we cover the functions of NIR-II FI that are promoted by the development of fluorophores, notably including its outlook on molecular imaging in vivo.

Cynaroside protects the blue light-induced retinal degeneration through alleviating apoptosis and inducing autophagy in vitro and in vivo.

BACKGROUND: Blue light can directly penetrate the lens and reach the retina to induce retinal damage, causing dry age-related macular degeneration (dAMD). Cynaroside (Cyn), a flavonoid glycoside, was proved to alleviate the oxidative damage of retinal cells in vitro. However, whether or not Cyn also exerts protective effect on blue light-induced retinal degeneration and its mechanisms of action are unclear. PURPOSE: This study aims to evaluate the protective effects of Cyn against blue-light induced retinal degeneration and its underlying mechanisms in vitro and in vivo. STUDY DESIGN/METHODS: Blue light-induced N-retinylidene-N-retinylethanolamine (A2E)-laden adult retinal pigment epithelial-19 (ARPE-19) cell damage and retinal damage in SD rats were respectively used to evaluate the protective effects of Cyn on retinal degeneration in vitro and in vivo. MTT assay and AnnexinV-PI double staining assay were used to evaluate the in vitro efficacy. Histological analysis, TUNEL assay, and fundus imaging were conducted to evaluate the in vivo efficacy. ELISA assay, western blot, and immunostaining were performed to investigate the mechanisms of action of Cyn. RESULTS: Cyn decreased the blue light-induced A2E-laden ARPE-19 cell damage and oxidative stress. Intravitreal injection of Cyn (2, 4 µg/eye) reversed the retinal degeneration induced by blue light in SD rats. Furthermore, Cyn inhibited the nuclear translocation of NF-κB and induced autophagy, which led to the clearance of overactivated pyrin domain containing 3 (NLRP3) inflammasome in vitro and in vivo. CONCLUSION: Cyn protects against blue light-induced retinal degeneration by modulating autophagy and decreasing the NLRP3 inflammasome.