Graphene Oxide and Polyelectrolyte Composed One-Way Expressway for Guiding Electron Transfer of Integrated Artificial Photosynthesis

A novel photocatalyst/biocatalyst integrated artificial photosynthesis system (APS) based on polyurethane hollow nanofibers doped with graphene oxide (GO) and poly­(allylamine hydrochloride) (PAH) was developed and employed for selective methanol conversion from CO₂. The biocatalysts, including formate, formaldehyde, and alcohol dehydrogenases, as well as NAD⁺, were <i>in situ</i> coencapsulated inside the lumen of the GO-PAH-doped PU nanofibers (G-Fiber) by simply predissolving them in the core-phase solution for coaxial electrospinning, while the precise assembling of the photocatalyst parts involving visible light active photosensitizer (PS) and electron mediator (M) on the surface of the G-Fiber was realized by their π–π interactions with the GO doped in the shell of fibers. By using this highly integrated APS, about 10-times higher methanol yield was accomplished as compared with the solution-based system. The significantly enhanced reaction efficiency of the G-Fiber-based APS is considered predominately due to the electron transfer “one-way expressway” composed of the doped polyelectrolyte and GO in the G-Fiber; therefore, the electron-transfer distance along the PS-M-NAD⁺ electron transport chain could be shortened and the speed could be accelerated. As a consequence, the electron back-flow between PS and M, as well as the recombination of the excited electron and the hole of PS were eliminated. The current work will represent a new benchmark for solar-energy driven conversion of CO₂ to a wide range of fuels and chemicals in an environmentally benign manner

In Situ Live-Cell Nucleus Fluorescence Labeling with Bioinspired Fluorescent Probes

Fluorescent imaging techniques for visualization of nuclear structure and function in live cells are fundamentally important for exploring major cellular events. The ideal cellular labeling method is capable of realizing label-free, in situ, real-time, and long-term nucleus labeling in live cells, which can fully obtain the nucleus-relative information and effectively alleviate negative effects of alien probes on cellular metabolism. However, current established fluorescent probes-based strategies (e.g., fluorescent proteins-, organic dyes-, fluorescent organic/inorganic nanoparticles-based imaging techniques) are unable to simultaneously realize label-free, in situ, long-term, and real-time nucleus labeling, resulting in inevitable difficulties in fully visualizing nuclear structure and function in live cells. To this end, we present a type of bioinspired fluorescent probes, which are highly efficacious for in situ and label-free tracking of nucleus in long-term and real-time manners. Typically, the bioinspired polydopamine (PDA) nanoparticles, served as fluorescent probes, can be readily synthesized in situ within live cell nucleus without any further modifications under physiological conditions (37 °C, pH ∼7.4). Compared with other conventional nuclear dyes (e.g., propidium iodide (PI), Hoechst), superior spectroscopic properties (e.g., quantum yield of ∼35.8% and high photostability) and low cytotoxicity of PDA-based probes enable long-term (e.g., 3 h) fluorescence tracking of nucleus. We also demonstrate the generality of this type of bioinspired fluorescent probes in different cell lines and complex biological samples

Fluorescent Silicon Nanorods-Based Ratiometric Sensors for Long-Term and Real-Time Measurements of Intracellular pH in Live Cells

Long-term and real-time investigation of the dynamic process of pH_i changes is critically significant for understanding the related pathogenesis of diseases and the design of intracellular drug delivery systems. Herein, we present a one-step synthetic strategy to construct ratiometric pH sensors, which are made of europium (Eu)-doped one-dimensional silicon nanorods (Eu@SiNRs). The as-prepared Eu@SiNRs have distinct emission maxima peaks at 470 and 620 nm under 405 nm excitation. Of particular note, the fluorescence emission intensity at 470 nm decreases along with the increase of pH, while the one at 620 nm is nearly unaffected by pH changes, making Eu@SiNRs a feasible probe for pH sensing ratiometrically. Moreover, Eu@SiNRs are found to be responsive to a broad pH range (ca. 3–9), biocompatible (e.g., ∼100% of cell viability during 24 h treatment) and photostable (e.g., ∼10% loss of intensity after 40 min continuous UV irradiation). Taking advantages of these merits, we employ Eu@SiNRs for the visualization of the cytoplasmic alkalization process mediated by nigericin in living cells, for around 30 min without interruption, revealing important information for understanding the dynamic process of pH_i fluctuations

Comprehensive Insights into the Multi-Antioxidative Mechanisms of Melanin Nanoparticles and Their Application To Protect Brain from Injury in Ischemic Stroke

Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for treating a myriad of important diseases through scavenging excessive reactive oxygen and nitrogen species (RONS), a mechanism critical in disease development and progression. However, similar to antioxidative enzymes, currently studied nanoantioxidants have demonstrated scavenging activity to specific RONS, and sufficient antioxidative effects against multiple RONS generated in diseases remain elusive. Here we propose to develop bioinspired melanin nanoparticles (MeNPs) for more potent and safer antioxidative therapy. While melanin is known to function as a potential radical scavenger, its antioxidative mechanisms are far from clear, and its applications for the treatment of RONS-associated diseases have yet to be well-explored. In this study, we provide for the first time exhaustive characterization of the activities of MeNPs against multiple RONS including O₂^•–, H₂O₂, ^•OH, ^•NO, and ONOO^–, the main toxic RONS generated in diseases. The potential of MeNPs for antioxidative therapy has also been evaluated <i>in vitro</i> and in a rat model of ischemic stroke. In addition to the broad defense against these RONS, MeNPs can also attenuate the RONS-triggered inflammatory responses through suppressing the expression of inflammatory mediators and cytokines. <i>In vivo</i> results further demonstrate that these unique multi-antioxidative, anti-inflammatory, and biocompatible features of MeNPs contribute to their effective protection of ischemic brains with negligible side effects

Photostable and Biocompatible Fluorescent Silicon Nanoparticles-Based Theranostic Probes for Simultaneous Imaging and Treatment of Ocular Neovascularization

Ocular neovascularization can result in devastating diseases that lead to marked vision impairment and eventual visual loss. In clinical implementation, neovascular eye diseases are first diagnosed by fluorescein angiography and then treated by multiple intravitreal injections, which nevertheless involves vision-threatening complications, as well as lack of real-time monitoring disease progression and timely assessment of therapeutic outcomes. To address this critical issue, we herein present a kind of theranostic agents made of peptide-functionalized silicon nanoparticles (SiNPs), suitable for simultaneous ocular neovascularization imaging and therapy. Typically, in addition to negligible toxicity and high specific binding ability to human retinal microvascular endothelial cells tube formation, the cyclo-(Arg-Gly-Asp-d-Tyr-Cys) (<i>c</i>-(RGDyC))-conjugated SiNPs (SiNPs-RGD) features efficacious antiangiogenic ability in wound healing migration, transwell migration, transwell invasion, and tube formation assays. Taking advantage of these unique merits, we further employ the SiNPs-RGD for labeling angiogenic blood vessels and neovascularization suppression, demonstrating obvious inhibition of new blood vessels formation in mouse corneas. These results suggest the SiNPs-RGD as a novel class of high-quality theranostic probes is suitable for simultaneous diagnosis and treatment in ocular neovascular diseases

Peptide-Conjugated Fluorescent Silicon Nanoparticles Enabling Simultaneous Tracking and Specific Destruction of Cancer Cells

We herein introduce a kind of fluorescent silicon nanoparticles (SiNPs) bioprobes, that is, peptides-conjugated SiNPs, which simultaneously feature small sizes (<10 nm), biological functionality, and stable and strong fluorescence (photoluminescent quantum yield (PLQY): ∼28%), as well as favorable biocompatibility. Taking advantage of these merits, we further demonstrate such resultant SiNPs bioprobes are superbly suitable for real-time immunofluorescence imaging of cancer cells. Meanwhile, malignant tumor cells could be specifically destroyed by the peptides-conjugated SiNPs, suggesting potential promise of simultaneous detection and treatment of cancer cells

Biomimetic Preparation and Dual-Color Bioimaging of Fluorescent Silicon Nanoparticles

Fluorescent silicon nanoparticles (SiNPs), as the most important zero-dimensional silicon nanostructures, hold high promise for long-awaited silicon-based optic applications. There currently remain major challenges for the green, inexpensive, and mass production of fluorescent SiNPs, resulting in difficulties in sufficiently exploiting the properties of these remarkable materials. Here, we show that fluorescent small-sized (∼3.8 nm) SiNPs can be produced through biomimetic synthesis in rapid (10 min), low-cost, and environmentally benign manners. The as-prepared SiNPs simultaneously feature bright fluorescence (quantum yield (QY), ∼15–20%), narrow emission spectral width (full width at half-maximum (fwhm), ∼30 nm), and nontoxicity, making them as high-quality fluorescent probes for biological imaging in vitro and in vivo

Large-Scale Aqueous Synthesis of Fluorescent and Biocompatible Silicon Nanoparticles and Their Use as Highly Photostable Biological Probes

A large-scale synthetic strategy is developed for facile one-pot aqueous synthesis of silicon nanoparticles (SiNPs) yielding ∼0.1 g SiNPs of small sizes (∼2.2 nm) in 10 min. The as-prepared SiNPs feature strong fluorescence (photoluminescence quantum yield of 20–25%), favorable biocompatibility, and robust photo- and pH-stability. Moreover, the SiNPs are naturally water dispersible, requiring no additional post-treatment. Such SiNPs can serve as highly photostable bioprobes and are superbly suitable for long-term immunofluorescent cellular imaging

Tumor Microenvironment-Responsive Multistaged Nanoplatform for Systemic RNAi and Cancer Therapy

While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, the effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core. When the rationally designed, long circulating polymeric NPs accumulate in tumor tissues after intravenous administration, the targeted siRNA-TCPA complexes can be rapidly released via TME pH-mediated NP disassembly for subsequent specific targeting of tumor cells and cytosolic transport, thus achieving efficient gene silencing. In vivo results further demonstrate that the multistaged NP delivery of siRNA against bromodomain 4 (BRD4), a recently discovered target protein that regulates the development and progression of prostate cancer (PCa), can significantly inhibit PCa tumor growth

Intracellular Mechanistic Understanding of 2D MoS₂ Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy

Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenide (TMD) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials (<i>i</i>.<i>e</i>., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS₂) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy. MoS₂ NSs were found to be internalized through three pathways: clathrin → early endosomes → lysosomes, caveolae → early endosomes → lysosomes, and macropinocytosis → late endosomes → lysosomes. We also observed autophagy-mediated accumulation in the lysosomes and exocytosis-induced efflux of MoS₂ NSs. Based on these findings, we developed a strategy to achieve effective and synergistic <i>in vivo</i> cancer therapy with MoS₂ NSs loaded with low doses of drug through inhibiting exocytosis pathway-induced loss. To the best of our knowledge, this is the first systematic experimental report on the nano-bio interaction of 2D nanomaterials in cells and their application for anti-exocytosis-enhanced synergistic cancer therapy