Protective Effect of Hydrogen on Sodium Iodate-Induced Age-Related Macular Degeneration in Mice

Oxidative stress is one of the main causes of AMD. Hydrogen has anti-oxidative stress and apoptotic effects on retinal injury. However, the effect of hydrogen on AMD is not clear. In this study, fundus radiography, OCT, and FFA demonstrated that HRW reduced the deposition of drusen-like structures in RPE layer, prevented retina from thinning and leakage of ocular fundus vasculature induced by NaIO3. ERG analysis confirmed that HRW effectively reversed the decrease of a-wave and b-wave amplitude in NaIO3-mice. Mechanistically, HRW greatly reduced the oxidative stress reaction through decreased MDA levels, increased SOD production, and decreased ROS content. The OGG1 expression was downregulated which is a marker of oxidative stress. Involvement of oxidative stress was confirmed using oxidative stress inhibitor ALCAR. Moreover, oxidative stress reaction was associated with expression of Sirt1 level and HRW significantly inhibited the downregulation of Sirt1 expression. This result was further confirmed with AICAR which restore Sirt1 expression and activity. In addition, NaIO3-induced retinal damage was related to apoptosis via caspase 8 and caspase 9, but not the caspase 3 pathways, which led to upregulation of Bax and p53, downregulation of Bcl-2, and increase in Jc-1-positive cells in mice. However, HRW effectively reversed these effects that apoptosis induced. These results suggest that HRW protects retinal functions against oxidative stress injury through inhibiting downregulation of Sirt1 and reducing retinal apoptosis. Therefore, we speculated that hydrogen administration is a promising treatment for AMD therapy

g‑C₃N₄ Coated Upconversion Nanoparticles for 808 nm Near-Infrared Light Triggered Phototherapy and Multiple Imaging

Exploring novel photosensitizer (PS) with good stability and high light converting efficiency and designing novel structure to integrate deep penetrating near-infrared (NIR) light excitable up-conversion nanoparticles (UCNPs) and PS into one system are highly fascinating in the photodynamic therapy (PDT) field. In this study, a novel core–shell structured platform (UCNPs@g-C₃N₄–PEG) with all-in-one “smart” functions for simultaneous photodynamic therapy, photothermal therapy (PTT), and trimodal imaging properties has been rationally designed and fabricated. This system is composed of a core–shell–shell structured NaGdF₄:Yb/Tm@NaGdF₄:Yb@NaNdF₄:Yb up-conversion luminescence (UCL) core and photoactive graphitic-phase carbon nitride (g-C₃N₄) mesoporous shell closely coated on individual core. This designed structure allows large specific surface area, high loading amount, close proximity to the UCL core, and almost no leakage of g-C₃N₄ PS, thus ensuring sufficient reactive oxygen species (ROS) to damage tumor cells. Excitation by 808 nm NIR light, the emitted ultraviolet, and visible light can activate g-C₃N₄ to generate significant amount of ROS and the doped Nd³⁺ ions give rise to obvious thermal effect, which leads to excellent antitumor efficiency due to the combined PDT and PTT effect. Considering the trimodal imaging properties (UCL, computed tomography, and magnetic resonance imaging), we achieved an imaging guided cancer phototherapy motivated by a single NIR laser

A Versatile Near Infrared Light Triggered Dual-Photosensitizer for Synchronous Bioimaging and Photodynamic Therapy

Photodynamic therapy (PDT) based on Tm³⁺-activated up-conversion nanoparticles (UCNPs) can effectively eliminate tumor cells by triggering inorganic photosensitizers to generate cytotoxic reactive oxygen species (ROS) upon tissue penetrating near-infrared (NIR) light irradiation. However, the partial use of the emitted lights from UCNPs greatly hinders their application. Here we develop a novel dual-photosensitizer nanoplatform by coating mesoporous graphitic-phase carbon nitride (g-C₃N₄) layer on UCNPs core, followed by attaching ultrasmall Au₂₅ nanoclusters and PEG molecules (named as UCNPs@g-C₃N₄–Au₂₅-PEG). The ultraviolet–visible (UV–vis) light and the intensive near infrared (NIR) emission from UCNPs can activate g-C₃N₄ and excite Au₂₅ nanoclusters to produce ROS, respectively, and thus realize the simultaneous activation of two kinds of photosensitizers for enhanced the efficiency of PDT mediated by a single NIR light excitation. A markedly higher PDT efficacy for the dual-photosensitizer system than any single modality has been verified by the enhanced ROS production and in vitro and in vivo results. By combining the inherent multi-imaging properties (up-conversion, CT, and MRI) of UCNPs, an imaging guided therapeutic platform has been built. As the first report of dual-inorganic-photosensitizer PDT agent, our developed system may be of high potential in future NIR light induced PDT application

Yolk-Structured Upconversion Nanoparticles with Biodegradable Silica Shell for FRET Sensing of Drug Release and Imaging-Guided Chemotherapy

Silica related nanovehicles are being widely studied for bioapplication, while the use <i>in vivo</i> has been restricted due to the biodegradation reluctance. Herein, a facile Mn-doping method was used to endow the upconversion nanoparticles (UCNPs) with a biodegradable shell, simply by transforming mesoporous silica coated UCNPs (UCNPs@mSiO₂) to Mn-doped upconversion nanocapsules (Mn-UCNCs). The yolk-structured Mn-UCNCs have huge internal space, which is greatly beneficial for DOX (a chemotherapeutic agent) storage. Furthermore, the Mn-doped nanoshell is responsive to mild reductive and acidic tumor condition, which enables the biodegradation of the silica shell in tumor sites and further accelerates the breakup of Si–O–Si bonds within the silica framework. This tumor-sensitive degradation of the shell not only facilitates DOX release in the tumor location but also allows faster nanoparticle diffusion and deeper tumor penetration, thus realizing efficient particle distribution and improved chemotherapy. Moreover, the biodegradability-enhanced DOX release brings a rapid recovery to the total emission intensity and a drastic decline to the red/green (R/G) ratio, which can be used to sense the drug release extent. The MRI effect caused by Mn release coupled with the inherent MRI/CT/UCL imaging derived from the UCNPs (NaGdF₄:Yb,Er@NaGdF₄:Yb) under NIR irradiation endow the nanocarrier with superior multiple imaging functions. The high biocompatibility of PEGylated Mn-UCNCs was validated, and the excellent anticancer effectiveness of the DOX loaded nanosystem was also achieved