Fluorescent Molecular Rotors for Viscosity Sensors.

Fluorescent molecular rotors (FMRs) can act as viscosity sensors in various media including subcellular organelles and microfluidic channels. In FMRs, the rotation of rotators connected to a fluorescent π-conjugated bridge is suppressed by increasing environmental viscosity, resulting in increasing fluorescence (FL) intensity. In this minireview, we describe recently developed FMRs including push-pull type π-conjugated chromophores, meso-phenyl (borondipyrromethene) (BODIPY) derivatives, dioxaborine derivatives, cyanine derivatives, and porphyrin derivatives whose FL mechanism is viscosity-responsive. In addition, FMR design strategies for addressing various issues (e.g., obtaining high FL contrast, internal FL references, and FL intensity-contrast trade-off) and their biological and microfluidic applications are also discussed.

Milk activates the expression of cytokines via Nrf2/HO-1 pathway in human periodontal ligament cells.

BACKGROUND: Milk is known as a suitable storage medium for avulsed teeth during emergency situations, but its potential toxicity on human periodontal ligament (PDL) cells has not been reported. The purpose of this study was to investigate the milk-induced gene profiles of PDL cells in vitro by microarray analysis after storage in milk. We additionally determined whether milk activates the cytoprotective defense mechanisms via the NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) pathway. MATERIAL AND METHODS: Gene induction in cultured human PDL cells after exposure to milk for 1 and 3 h as compared with non-treated PDL cells was analyzed by microarray analysis and subsequent RT-PCR. Reactive oxygen species (ROS) and Western blot analysis were used to determine whether milk activates the cytoprotective defense mechanisms using the Nrf2 and HO-1 pathway. RESULT: Microarray data analysis identified 868 (1 h per control) and 1782 (3 h per control) differentially expressed genes related to the duration of storage in milk. Exposure to milk for 3 and 1 h resulted in the upregulation of specific inflammatory cytokines, chemokines, and MMPs concomitant with downregulation of extracellular matrix-related genes. Exposure to milk increased the expression of peroxiredoxin-1, thioredoxin-1 and heme oxygenase (HO)-1 and stimulated the nuclear translocation of Nrf2. HO-1 inhibitor and Nrf2 siRNA blocked the milk-induced inflammatory response such as production of ROS, expression of cytokines, chemokines, and MMPs. CONCLUSION: Within the limit of this study, this study demonstrates that exposure of PDL cells to milk is associated with an upregulated expression of several pro-inflammatory proteins and key antioxidant proteins via the activation of Nrf2/ARE pathway in PDL cells.

Nanopore surface engineering of molecular imprinted mesoporous organosilica for rapid and selective detection of L-thyroxine.

To develop a biosensing platform for precise diagnosis and management of thyroid-related diseases, the sensitive and selective recognition and identification of L-thyroxine (T4), a thyroid hormone, remains challenging. We herein introduce T4-imprinted mesoporous organosilica (T4-IMO) for sensitive and specific detection of T4 via the sophisticated engineering of pore surfaces using additives with different polarities. The pore surface of T4-IMO emitting a stable fluorescence signal is simply modified by fixed additives. Additives embedded in the pore surface promote the rebinding response of T4 into the recognized cavities, subsequently sensitizing T4 detection. Notably, T4-IMO containing abundant fluorine elements on the pore surface shows a high affinity toward T4, remarkably boosting the rebinding capacity. In addition to good selectivity to T4, the "turn-off" fluorescent signal exhibits a linear relationship with the logarithm of T4 concentration in a range of 0-500 nM with a detection limit of 0.47 nM in synthetic urine samples. Our findings can establish an insightful strategy for the rational design of molecular-recognition-based sensor systems for the selective and sensitive detection of target analytes.

Aggregation-induced emission nanoparticles with improved optical absorption for boosting fluorescence signal of tumors in vivo.

Nanomaterial development has been extensively investigated for several decades to realize sensitive and accurate imaging of tumors in vivo. The manufacturing of nanoparticles with highly efficient tumor targeting and excellent optical properties is still an important research topic. The structure and composition ratio of materials that decisively contribute to the brightness and size of nanoparticles have a great influence on image sensitivity and tumor targeting efficiency. In this study, we developed aggregation-induced emission (AIE) nanoparticles with a widened light absorption window (nanoPMeOCN/BDP) to enable sensitive in vivo tumor imaging. The signal of nanoparticles is enhanced by integrating a high-density AIE polymer (PMeOCN) and light-absorbing fluorescent dye (BDP) in a nanoscopic space. BDP not only improves the light absorption of particles but also enhances the fluorescence signal of particles by effectively transferring absorbed energy to PMeOCN. The physically blended nanoPMeOCN/BDP show strong light absorption and improved sensitivity for the imaging of biological tissues because of their excellent optical performance compared to nanoPMeOCN of similar nanosizes (∼19 nm in size). In vivo imaging results further confirm that nanoPMeOCN/BDP can provide amplified signals with the successful accumulation of tumor tissue through the enhanced permeability and retention effect. We expect that the design strategy of nanoparticles with improved light absorption will provide a simple and general method for improving the accuracy of disease diagnosis.

Data on characterization and electrochemical analysis of zinc oxide and tungsten trioxide as counter electrodes for electrochromic devices.

The data presented in this article are related to a research paper entitled "Implementation of High-Performance Electrochromic Device Based on All-Solution-Fabricated Prussian Blue and Tungsten Trioxide Thin Film"[1]. Zinc oxide nanowire (ZnNW) and tungsten trioxide (WO3) were fabricated by different electrodeposition methods and characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and used as counter electrodes. The electrochromic (EC) properties of these devices were characterized using optoelectronic analysis during electrochemical applications.

Chemiluminescence imaging of Duox2-derived hydrogen peroxide for longitudinal visualization of biological response to viral infection in nasal mucosa.

Rationale: Hydrogen peroxide (H2O2) provides an important mechanism for resisting infectious pathogens within the respiratory tract, and accordingly, the in situ analysis of H2O2 generation in real time provides a valuable tool for assessing immune response. Methods: In this study, we applied a chemiluminescent nanoparticle-based real-time imaging approach to noninvasive evaluation of the Duox2-mediated H2O2 generation after viral infection, and assessed its usefulness for analytical purposes in mouse nasal mucosa. The chemiluminescent nanoprobe employed herein (BioNT) possesses appropriate physicochemical properties, such as high sensitivity and selectivity toward H2O2, no background noise, deliverability to the respiratory tract, and capability of multiple injections to a single animal subject for long-term repetitive imaging. Results: The favorable characteristics of BioNT allowed for a longitudinal study with the same mice to noninvasively evaluate the long-term evolution of endogenous H2O2 in the nasal epithelium after infection with influenza A virus (WS/33/H1N1). We found that nasal epithelial cells by themselves respond to viral infection by generating H2O2, and that the in vivo cumulative H2O2 level in the nasal mucosa peaks at day 3 post-infection. Such in vitro and in vivo temporal behaviors of the endogenous H2O2 generation showed a good correlation with those of Duox2 expression after infection. This correlation could be further confirmed with Duox2-deficient subjects (Duox2-knockdown NHNE cells and Duox2-knockout mutant mice) where no H2O2-induced chemiluminescence was detectable even after viral infection. Importantly, upon knock-down of Duox2 expression, the condition of mice caused by viral infection in the upper airway was significantly aggravated, evidencing the involvement of Duox2 in the immune defense. Conclusion: All these results reveal a critical role of Duox2 in the infection-induced H2O2 production and the H2O2-mediated immune response to infection in the respiratory tract, well elucidating the potential of BioNT as a noninvasive tool for fundamental in vivo studies of infectious diseases.

A fluorogenic molecular nanoprobe with an engineered internal environment for sensitive and selective detection of biological hydrogen sulfide.

A nanoreactor approach based on the amphiphilic assembly of various molecules offers a chance to finely engineer the internal reaction medium to enable highly selective and sensitive detection of H2S in biological media, being useful for microscopic imaging of cellular processes and in vitro diagnostics with blood samples.

Rational design for enhancing inflammation-responsive in vivo chemiluminescence via nanophotonic energy relay to near-infrared AIE-active conjugated polymer.

H2O2-specific peroxalate chemiluminescence is recognized as a potential signal for sensitive in vivo imaging of inflammation but the effect of underlying peroxalate-emitter energetics on its efficiency has rarely been understood. Here we report a simple nanophotonic way of boosting near-infrared chemiluminescence with no need of complicated structural design and synthesis of an energetically favored emitter. The signal enhancement was attained from the construction of a nanoparticle imaging probe (∼26 nm in size) by dense nanointegration of multiple molecules possessing unique photonic features, i.e., i) a peroxalate as a chemical fuel generating electronic excitation energy in response to inflammatory H2O2, ii) a low-bandgap conjugated polymer as a bright near-infrared emitter showing aggregation-induced emission (AIE), and iii) an energy gap-bridging photonic molecule that relays the chemically generated excitation energy to the emitter for its efficient excitation. From static and kinetic spectroscopic studies, a green-emissive BODIPY dye has proven to be an efficient relay molecule to bridge the energy gap between the AIE polymer and the chemically generated excited intermediate of H2O2-reacted peroxalates. The energy-relayed nanointegration of AIE polymer and peroxalate in water showed a 50-times boosted sensing signal compared to their dissolved mixture in THF. Besides the high H2O2 detectability down to 10(-9) M, the boosted chemiluminescence presented a fairly high tissue penetration depth (>12 mm) in an ex vivo condition, which enabled deep imaging of inflammatory H2O2 in a hair-covered mouse model of peritonitis.

Low-bandgap biophotonic nanoblend: a platform for systemic disease targeting and functional imaging.

Photonic nanomaterials have found wide applications in theranostics. We introduce here a design of all-organic photonic nanoparticles, different from traditional ones, in which we utilize nanoblend of a low-bandgap π-conjugated polymer (LB-CP) and polystyrene as the photonic core, surrounded by an FDA-approved polymeric surfactant. This design provides capability for efficient deep tissue imaging using highly penetrating near-infrared (NIR) excitation and emission of LB-CP and also allows us to incorporate a NIR phosphorescent oxygen-sensitive dye in the core to serve as a dual-emissive probe for hypoxia imaging. These biophotonic nanoblend (BNB) particles (∼20 nm in diameter) show facile blood circulation, efficient disease targeting and minimal liver filtration as well as sustained renal excretion in the intravenously administered mouse models, as noninvasively visualized by the NIR emission signals. In diseased mouse models, pathological tissue deoxygenation at hypoxic sites was successfully detected with ratiometric spectral information. We also show that our nanoformulation exhibits no apparent toxicity, thus serving as a versatile biophotonics platform for diagnostic imaging.

Biolighted Nanotorch Capable of Systemic Self-Delivery and Diagnostic Imaging.

Sensitive imaging of inflammation with a background-free chemiluminescence (CL) signal has great potential as a clinically relevant way of early diagnosis for various inflammatory diseases. However, to date, its feasibility has been limitedly demonstrated in vivo with locally induced inflammation models by in situ injection of CL probes. To enable systemic disease targeting and imaging by intravenous administration of CL probes, hurdles need to be overcome such as weak CL emission, short glowing duration, or inability of long blood circulation. Here, we report a CL nanoprobe (BioNT) that surmounted such limitations to perform precise identification of inflammation by systemic self-delivery to the pathological tissues. This BioNT probe was engineered by physical nanointegration of multiple kinds of functional molecules into the ultrafine nanoreactor structure (∼15 nm in size) that combines solid-state fluorescence-induced enhanced peroxalate CL and built-in machinery to control the intraparticle kinetics of CL reaction. Upon intravenous injection into a normal mouse, BioNT showed facile blood circulation and generated a self-lighted strong CL torchlight throughout the whole body owing to the tiny colloidal structure with an antifouling surface as well as high CL sensitivity toward endogenous biological hydrogen peroxide (H2O2). In mouse models of local and systemic inflammations, blood-injected BioNT visualized precise locations of inflamed tissues with dual selectivity (selective probe accumulation and selective CL reaction with H2O2 overproduced by inflammation). Even a tumor model that demands a long blood circulation time for targeting (>3 h) could be accurately identified by persistent signaling from the kinetics-tailored BioNT with a 65-fold slowed CL decay rate. We also show that BioNT exhibits no apparent toxicity, thus holding potential for high-contrast diagnostic imaging.

Nanophotosensitizers toward advanced photodynamic therapy of Cancer.

UNLABELLED: Photodynamic therapy (PDT) is a non-invasive treatment modality for selective destruction of cancer and other diseases and involves the colocalization of light, oxygen, and a photosensitizer (PS) to achieve photocytotoxicity. Although this therapeutic method has considerably improved the quality of life and life expectancy of cancer patients, further advances in selectivity and therapeutic efficacy are required to overcome numerous side effects related to classical PDT. The application of nanoscale photosensitizers (NPSs) comprising molecular PSs and nanocarriers with or without other biological/photophysical functions is a promising approach for improving PDT. In this review, we focus on four nanomedical approaches for advanced PDT: (1) nanocarriers for targeted delivery of PS, (2) introduction of active targeting moieties for disease-specific PDT, (3) stimulus-responsive NPSs for selective PDT, and (4) photophysical improvements in NPS for enhanced PDT efficacy. HIGHLIGHTS: ► Conservation of normal tissues demands non-invasive therapeutic methods. ► PDT is a light-activated, non-invasive modality for selective destruction of cancers.► Success of PDT requires further advances to overcome the limitations of classical PDT. ►Nanophotosensitizers help improve target selectivity and therapeutic efficacy of PDT.