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

Up-Conversion Luminescence Properties of Lanthanide-Gold Hybrid Nanoparticles as Analyzed with Discrete Dipole Approximation

Up-conversion nanoparticles (UCNP) under near-infrared (NIR) light irradiation have been well investigated in the field of bio-imaging. However, the low up-conversion luminescence (UCL) intensity limits applications. Plasmonic modulation has been proposed as an effective tool to adjust the luminescence intensity and lifetime. In this study discrete dipole approximation (DDA) was explored concerning guiding the design of UCNP@mSiO2-Au structures with enhanced UCL intensity. The extinction effects of gold shells could be changed by adjusting the distance between the UCNPs and the Au NPs by synthesized tunable mesoporous silica (mSiO2) spacers. Enhanced UCL was obtained under 808 nm irradiation. The original theoretical predictions could not be demonstrated to full extend by experimental data, indicating that better models for simulation need to take into account in homogeneities in particle morphologies. Yet, one very certain conclusion resulting from the DDA calculations and experiments is that the absorbance can blue-shift with more Au NPs added and the absorbance can-red shift for samples with enhanced silica sizes in the UCNP@mSiO2-Au structures. Furthermore, when the DDA model is more consistent with the practical structure (dispersed Au NPs instead of Au shell), the theoretical absorbance occurs almost the same as the practical absorbance. All in all, the DDA could fit the extinction effect of Au perfectly and be suitable for guiding how to design the UCNP and Au

Hollow Structured Y₂O₃:Yb/Er–Cu_<i>x</i>S Nanospheres with Controllable Size for Simultaneous Chemo/Photothermal Therapy and Bioimaging

To integrate photothermal therapy (PTT) with chemotherapy for improved antitumor efficiency, we designed a novel multifunctional composite by attaching Cu_<i>x</i>S nanoparticles onto the surface of Y₂O₃:Yb/Er hollow spheres through a combined coprecipitation and subsequent hydrothermal route. By altering the initial pH values for the synthesis of precursors, the size and structure properties of the final composites can controllably be tuned. The conjugated folic acid (FA) makes the composite recognize the targeted cancer cells and the attached Cu_<i>x</i>S nanoparticles endow the composite with photothermal function. It is found that the release of doxorubicin (DOX) from the functional carrier could be triggered by both pH value and near-infrared (NIR) radiation. In particular, both PTT and chemotherapy can be simultaneously driven by 980 nm laser irradiation. The synergistic therapeutic effect based on PTT and chemotherapy can lead to low in vitro viability of 12.9% and highly strong inhibition of animal H22 tumor in vivo, which is superior to any individual therapy. Moreover, the composite exhibits the clear in vivo red up-conversion luminescence (UCL). This multifunctional nanocarrier can be applicable as bioimaging agent and effective antitumor agent for the synergistic interaction between PTT and the enhanced chemotherapy

<i>In Situ</i> Growth Strategy to Integrate Up-Conversion Nanoparticles with Ultrasmall CuS for Photothermal Theranostics

In the theranostic field, a near-infrared (NIR) laser is located in the optical window, and up-conversion nanoparticles (UCNPs) could be potentially utilized as the imaging agents with high contrast. Meanwhile, copper sulfide (CuS) has been proposed as a photothermal agent with increased temperature under a NIR laser. However, there is still no direct and effective strategy to integrate the hydrophobic UCNPs with CuS until now. Herein, we propose an <i>in situ</i> growth routine based on the hydrophobic core/shell UCNPs combined with ultrasmall water-soluble CuS triggered by single 808 nm NIR irradiation as the theranostic platform. Hydrophobic NaYF₄:Yb,Er@NaYF₄,Nd,Yb could be turned hydrophilic with highly dispersed and biocompatible properties through conjunction with transferred dopamine. The as-synthesized ultrasmall CuS (3 and 7 nm) served as a stable photothermal agent even after several laser-on/off cycles. Most importantly, comparing with the mix routine, the <i>in situ</i> growth routine to coat UCNPs with CuS is meaningful, and the platform is uniform and stable. Green luminescence-guided hyperthermia could be achieved under a single 808 nm laser, which was evidenced by <i>in vitro</i> and <i>in vivo</i> assays. This nanoplatform is applicable as a bioimaging and photothermal antitumor agent, and the <i>in situ</i> growth routine could be spread to other integration processes

Lutecium Fluoride Hollow Mesoporous Spheres with Enhanced Up-Conversion Luminescent Bioimaging and Light-Triggered Drug Release by Gold Nanocrystals

Uniform Na₅Lu₉F₃₂ hollow mesoporous spheres (HMSs) have been successfully prepared by a facile and mild (50 °C for 5 h) coprecipitation process, and Au nanocrystals (NCs) with particle size of about 10 nm were conjugated to poly­(ether imide) (PEI) modified HMSs by electrostatic interaction. Compared with Na₅Lu₉F₃₂:Yb/Er HMSs, the up-conversion (UC) luminescence intensity of Na₅Lu₉F₃₂:Yb/Er@Au HMSs was much higher under low pump power due to the local field enhancement (LFE) of Au NCs, and there is a surface plasmon resonance (SPR) effect with nonradiative transitions which generates a thermal effect. These two effects have been proved by theoretical discrete-dipole approximation (DDA) simulation. The good biocompatibility of Na₅Lu₉F₃₂:Yb/Er@Au HMSs indicates them as a promising candidate in the biological field. Particularly, under near-infrared (NIR) laser irradiation, a rapid doxorubicin (DOX) release was achieved due to the thermal effect of Au NCs. In this case, Na₅Lu₉F₃₂:Yb/Er@Au HMSs exhibit an apparent NIR light-controlled “on/off” drug release pattern. In addition, UC luminescent images uptaken by cells show brighter green and red emission under NIR laser excitation. Therefore, this novel multifunctional (mesoporous, enhanced UC luminescent, and light-triggered drug release) material should be potential as a suitable targeted cancer therapy carrier and bioimaging

Imaging-Guided and Light-Triggered Chemo-/Photodynamic/Photothermal Therapy Based on Gd (III) Chelated Mesoporous Silica Hybrid Spheres

Exploring a combined anticancer therapeutic strategy to overcome the limitations of a single mode and pursue higher therapeutic efficiency is highly promising in both fundamental and clinical investigations. Herein, a theranostic nanoplatform based on mesoporous silica, which is functionalized by hybrid nanosphere photosensitizer Chlorin e6 (Ce6), photothermal agent carbon dots (CDs), and imaging agent Gd (III) ions has been rationally designed and fabricated. A thermo/pH-coupling sensitive polymer (P­(NIPAm-<i>co</i>-MAA)) coated on a composite acted as a key “gatekeeper” to control drug release at the appropriate time and location. Upon light irradiation, two-mode synergistic therapeutic effect of photodynamic and photothermal therapy can be achieved by photoactive Ce6 and CDs. Meanwhile, the CDs loaded in the channels of mesoporous silica hybrid spheres can also play a role in handling the “gatekeeper” polymer to control the drug release process. Combined with the thermo/pH-sensitive drug release-induced controllable chemotherapy, this platform shows synergistic therapeutic efficacy better than any single/dual therapy, which is confirmed with evidence from in vivo and in vitro assays. Considering the chelated Gd³⁺ simultaneously introduced magnetic resonance imaging (MRI) and computed tomography (CT) properties, this multifunctional platform should have excellent potential in the imaging-guided cancer therapy field

A Single 808 nm Near-Infrared Light-Mediated Multiple Imaging and Photodynamic Therapy Based on Titania Coupled Upconversion Nanoparticles

To solve the issue of limited penetration depth and overheating of the excited 980 nm near-infrared (NIR) light, and unstable and insufficient loading amount of photosensitizers (PSs) in photodynamic therapy (PDT), we have constructed a well-defined core–shell structured NaGdF₄:Yb/Tm@NaGdF₄:Yb@NaNdF₄:Yb@NaGdF₄@mSiO₂@TiO₂ (UCNPs@mSiO₂@TiO₂) nanocomposite by coating a layer of TiO₂ PSs/photocatalyst on an effective 808 nm-to-UV/visible upconversion luminescent (UCL) core to achieve simultaneous multiple bioimaging and efficient PDT. The design of quenching-shield layer can eliminate the back energy transfer from activator Tm³⁺ to sensitized Nd³⁺, thus significantly improving the UCL emission. The high surface area of mesoporous silica-coated UCNPs facilitates the stable and high loading amount of anatase TiO₂. In vivo results indicate that 808 nm NIR light-mediated PDT using UCNPs@mSiO₂@TiO₂ as photosensitizers shows much higher antitumor efficacy than those with 980 nm and UV irradiations due to the higher tissue penetration depth. Meanwhile, the platform itself as an imaging nanoprobe endows the sample with multiple imaging (UCL/CT/MRI) properties. Our work makes great progress toward the integrity of diagnosis and PDT induced by a single 808 nm NIR light