Neodymium-Sensitized Nanoconstructs for Near-Infrared Enabled Photomedicine.

Neodymium (Nd3+ )-sensitized nanoconstructs have gained increasing attention in recent decades due to their unique properties, especially optical properties. The design of various Nd3+ -sensitized nanosystems is expected to contribute to medical and health applications, due to their advantageous properties such as high penetration depth, excellent photostability, non-photobleaching, low cytotoxicity, etc. However, the low conversion efficiency and potential long-term toxicity of Nd3+ -sensitized nanoconstructs are huge obstacles to their clinical translations. This review article summarizes three energy transfer pathways of all kinds of Nd3+ -sensitized nanoconstructs focusing on the properties of Nd3+ ions and discusses their recent potential applications as near-infrared (NIR) enabled photomedicine. This review article will contribute to the design and fabrication of novel Nd3+ -sensitized nanoconstructs for NIR-enabled photomedicine, aiming for potentially safer and more efficient designs to get closer to clinical usage.

Upconversion Nanoparticles-Based Multiplex Protein Activation to Neuron Ablation for Locomotion Regulation.

The optogenetic neuron ablation approach enables noninvasive remote decoding of specific neuron function within a complex living organism in high spatiotemporal resolution. However, it suffers from shallow tissue penetration of visible light with low ablation efficiency. This study reports a upconversion nanoparticle (UCNP)-based multiplex proteins activation tool to ablate deep-tissue neurons for locomotion modulation. By optimizing the dopant contents and nanoarchitecure, over 300-fold enhancement of blue (450-470 nm) and red (590-610 nm) emissions from UCNPs is achieved upon 808 nm irradiation. Such emissions simultaneously activate mini singlet oxygen generator and Chrimson, leading to boosted near infrared (NIR) light-induced neuronal ablation efficiency due to the synergism between singlet oxygen generation and intracellular Ca2+ elevation. The loss of neurons severely inhibits reverse locomotion, revealing the instructive role of neurons in controlling motor activity. The deep penetrance NIR light makes the current system feasible for in vivo deep-tissue neuron elimination. The results not only provide a rapidly adoptable platform to efficient photoablate single- and multiple-cells, but also define the neural circuits underlying behavior, with potential for development of remote therapy in diseases.

Generating New Cross-Relaxation Pathways by Coating Prussian Blue on NaNdF4 To Fabricate Enhanced Photothermal Agents.

Cross-relaxation among sensitizers is commonly regarded as deleterious in fluorescent materials, although favorable in photothermal agents. Herein, we coated Prussian blue (PB) on NaNdF4 nanoparticles to fabricate core-shell nanocomplexes with new cross relaxation pathways between the ladder-like energy levels of Nd3+ ions and continuous energy band of PB. The photothermal conversion efficiency was improved exceptionally and the mechanism of the enhanced photothermal effect was investigated. In vivo photoacoustic imaging and photothermal therapy demonstrated the potential of the enhanced photothermal agents. Moreover, the concept of generating new cross-relaxation pathways between different materials is proposed to contribute to the design of all kinds of enhanced photothermal agents.

Determination of solubility parameters of ionic liquids and ionic liquid/solvent mixtures from intrinsic viscosity.

The total and partial solubility parameters (dispersion, polar and hydrogen-bonding solubility parameters) of ten ionic liquids were determined. Intrinsic viscosity approaches were used that encompassed a one-dimensional method (1D-Method), and two different three-dimensional methods (3D-Method1 and 3D-Method2). The effect of solvent type, the dimethylacetamide (DMA) fraction in the ionic liquid, and dissolution temperature on solubility parameters were also investigated. For all types of effect, both the 1D-Method and 3D-Method2 present the same trend in the total solubility parameter. The partial solubility parameters are influenced by the cation and anion of the ionic liquid. Considering the effect on partial solubility parameters of the solvent type in the ionic liquid, it was observed that in both 3D methods, the dispersion and polar parameters of a 1-ethyl-3-methylimidazolium acetate/solvent (60:40 vol %) mixture tend to increase as the total solubility parameter of the solvent increases.

Enantioselective separation of dansyl-DL-amino acids and some racemates on "click" functionalized native α-cyclodextrin based sub-2 µm columns.

The current work demonstrates that native α-cyclodextrin, anchored onto sub-2 µm silica particles via "click" reactions and packed into a 5 cm column, was found to be effective for the resolution of 11 pairs of dansyl-DL-amino acids (DAAs) using ultra-high performance liquid chromatography (UHPLC). All DAAs were completely or partially separated on the column and the resolution achieved for 7 pairs of DAAs was significantly greater than 1.5. It was found that the buffer type exerted a profound impact on the separation. The effects of analyte substituents adjacent to the chiral center of analytes as well as operation conditions with respect to the separation efficiency were discussed. Five racemic compounds with single or double rings also got resolved on this short α-CD column to some extent.

Cytotoxicity of hydroxyapatite nanoparticles is shape and cell dependent.

Nanosized hydroxyapatite (nHA) has been proposed as drug delivery vehicles because of its biocompatibility. While the possible risks of nHA inducing inflammation have been highlighted, the specific influence of varying nHA particle morphology is still unclear. In order to establish this understanding, nHA of four different shapes--needle (nHA-ND), plate (nHA-PL), sphere (nHA-SP) and rod (nHA-RD)--were synthesized. The particle effects with the concentration of 10-300 µg/mL on cytotoxicity, oxygen species generation, production of inflammatory cytokines (TNF-α and IL-6), particle-cell association and cellular uptake were evaluated on BEAS-2B and RAW264.7 cells. Results show that nHA-ND and nHA-PL induced the most significant cell death in BEAS-2B cultures compared to nHA-SP and nHA-RD. Necrosis-apoptosis assay by FITC Annexin V and propidium iodide (PI) staining revealed loss of the majority of BEAS-2B by necrosis. No significant cell death was recorded in RAW264.7 cultures exposed to any of the nHA groups. Correspondingly, no significant differences were observed in TNF-α level for RAW264.7 cells upon incubation with nHA of different shapes. In addition, nHA-RD exhibited a higher degree of particle-cell association and internalization in both BEAS-2B and RAW264.7 cells, compared to nHA-ND. The phenomena suggested that higher particle-cell association and increased cellular uptake of nHA need not result in increased cytotoxicity, indicating the importance of particle shape on cytotoxicity. Specifically, needle- and plate-shaped nHA induced the most significant cell-specific cytotoxicity and IL-6 expression but showed the least particle-cell association. Taken collectively, we demonstrated the shape-dependent effects of nHA on cytotoxicity, inflammatory cytokine expression and particle-cell association.

Architecture engineering of hierarchically porous chitosan/vacuum-stripped graphene scaffold as bioanode for high performance microbial fuel cell.

The bioanode is the defining feature of microbial fuel cell (MFC) technology and often limits its performance. In the current work, we report the engineering of a novel hierarchically porous architecture as an efficient bioanode, consisting of biocompatible chitosan and vacuum-stripped graphene (CHI/VSG). With the hierarchical pores and unique VSG, an optimized bioanode delivered a remarkable maximum power density of 1530 mW m(-2) in a mediator-less MFC, 78 times higher than a carbon cloth anode.

Hybrid Organic-Inorganic Perovskite Superstructures for Ultrapure Green Emissions.

All inorganic CsPbBr3 superstructures (SSs) have attracted much research interest due to their unique photophysical properties, such as their large emission red-shifts and super-radiant burst emissions. These properties are of particular interest in displays, lasers and photodetectors. Currently, the best-performing perovskite optoelectronic devices incorporate organic cations (methylammonium (MA), formamidinium (FA)), however, hybrid organic-inorganic perovskite SSs have not yet been investigated. This work is the first to report on the synthesis and photophysical characterization of APbBr3 (A = MA, FA, Cs) perovskite SSs using a facile ligand-assisted reprecipitation method. At higher concentrations, the hybrid organic-inorganic MA/FAPbBr3 nanocrystals self-assemble into SSs and produce red-shifted ultrapure green emissions, meeting the requirement of Rec. 2020 displays. We hope that this work will be seminal in advancing the exploration of perovskite SSs using mixed cation groups to further improve their optoelectronic applications.

Scar prevention through topical delivery of gelatin-tyramine-siSPARC nanoplex loaded in dissolvable hyaluronic acid microneedle patch across skin barrier.

Currently, there is no effective method to prevent the formation of hypertrophic scars and keloids, which can cause severe physical and psychological burdens to patients. Secreted protein acidic and cysteine-rich (SPARC) is involved in wound fibrosis by modulating fibroblast functions, causing excessive collagen deposition during wound healing. Thus, the reduction in SPARC gene expression after wounding can contribute to the downstream reduction in collagen production at the wound site and prevent scar formation. In this study, a dissolvable and biocompatible hyaluronic acid (HA) microneedle patch loaded with nanoplexes containing tyramine-modified gelatin and siRNA for SPARC (siSPARC/Gtn-Tyr) was investigated for topical scar prevention. Tyramine-modified gelatin (Gtn-Tyr) provides electrostatic protection and enhances cell internalization for siSPARC. In vitro studies using human dermal fibroblasts showed that both siSPARC/Gtn-Tyr nanoplexes and siSPARC/Gtn-Tyr-loaded microneedle patches can significantly reduce SPARC gene expression (P < 0.05) and do not cause discernable cytotoxic effects. Further studies using a mouse wound model demonstrate that the siSPARC/Gtn-Tyr-loaded microneedle patch can reduce collagen production during wound healing without triggering an immune response. When Gtn-Tyr-siSPARC is administered transdermally at the wound site, effective collagen reduction is achieved through silencing of the matricellular SPARC protein, thus promising the reduction of scar formation. Overall, the siSPARC/Gtn-Tyr loaded microneedle patch can potentially provide an effective transdermal anti-fibrotic treatment.

Enantioseparation of dansyl amino acids by ultra-high pressure liquid chromatography using cationic ß-cyclodextrins as chiral additives.

This work reports the application of ultra-high pressure liquid chromatography (UHPLC) for reasonably fast enantiorecognition of some dansyl amino acids by employing three cationic ß-cyclodextrins (ß-CDs) as chiral additives. Good resolutions were obtained on an Agilent C18 column (2.1 mm i.d.; 1.8 µm; 50 mm length) with 1% (v/v) triethylammonium acetate buffered at pH 4.7 and acetonitrile as the mobile phase. Most of the analytes could be baseline resolved within 10 min. Increased cationic CD concentration or acetonitrile proportion in the mobile phase results in a decreased retention factor but accentuated selectivity. Furthermore, molecular mechanics calculation was performed and found to be consistent with the experimental results.

Near-infrared-II activated inorganic photothermal nanomedicines.

The emergence of near-infrared-II (NIR-II) activated photomedicines has extended the penetration depth for noninvasive theranostics, especially for photothermal nanomedicines. The current early development stage for NIR-II activated photomedicines has focused on creating a greater variety of photothermal agents (PTAs) with superior photothermal conversion ability. However, there is no thorough review for NIR-II inorganic PTAs and most comparisons of the photothermal performances of NIR-II inorganic PTAs are made with NIR-I PTAs. This review will first discuss about the key mechanisms of NIR-II absorption and photothermal conversion. Subsequently, this review will summarize recently developed advanced NIR-II inorganic PTAs based on the dominant inorganic elements and provide a comparison of their NIR-II photothermal performances. The nanostructure design, enhancement strategies and potential biomedical applications will be listed and discussed. We hope this review will further inspire active development and study of NIR-II activated inorganic PTAs with good photothermal conversion ability, multifunctionality, biocompatibility or biodegradability, and disease targeting ability.

Monodispersed submicron porous silica particles functionalized with CD derivatives for chiral CEC.

Rapid and efficient enantioseparation of halogen aryl alcohols and beta-blockers propranolol and pindolol in packed bed CEC (p-CEC) using as-prepared submicron porous silica chiral stationary phases (CSPs) has been achieved. Monodispersed 0.66 and 0.81 microm chiral submicron porous silica spheres were prepared using tetramethoxysilane and hexadecyltrimethylammonium bromide, followed by a hydrothermal treatment method with ammonia-ethanol to expand the pore of silica spheres without changing their spherical morphology. A proper specific surface of ca. 230 m(2)/g and pore sizes average of 6-8 nm were obtained by this method. The submicron porous silica spheres were modified with mono-6-phenylcarbamoylated beta-CD via thiol-en radical addition. They were packed into 9 cm 50 microm id capillary columns with photopolymerized monolithic frits. These submicron CSPs showed greater column efficiency (about 476 000 plates/m for 4-iodophenyl-1-ethanol) and higher resolution than the corresponding 3 microm CSP.

Functional and multifunctional nanoparticles for bioimaging and biosensing.

Herein, we describe the synthesis of functional and multifunctional nanoparticles (NPs), derived from our recent work, for bioimaging and biosensing applications. The functionalized NPs involve quantum dots (QDs), magnetic particles (MPs) and noble metal NPs for the aforementioned applications. A diverse silica coating approaches (reverse microemulsion and thin silanization) are delineated for the design of water-soluble NPs. We also review the synthesis of silica-coated bifunctional NPs consisting of MPs and QDs for live cell imaging of human liver cancer cells (HepG2) and mouse fibroblast cells (NIH-3T3). Using silica coated NPs, various NPs that are functionalized with antibody, oligonucleotide, biotin and dextran are efficiently used for protein detection.

Gadolinium oxide ultranarrow nanorods as multimodal contrast agents for optical and magnetic resonance imaging.

We demonstrate a simple synthetic strategy for the fabrication of single-phase rare earth (RE) doped gadolinium oxide (Gd(2)O(3):RE where RE = terbium (Tb), ytterbium (Yb), and erbium (Er)) nanorods (NRs) as multimodal imaging probes. The NRs are ultranarrow and exhibit both emission and magnetic characteristics. The Tb-doped and Yb/Er-codoped Gd(2)O(3) NRs exhibit down- and up-conversion fluorescence respectively, and also exhibit paramagnetism. Importantly, these codoped NRs possess excellent magnetic characteristics, as shown in their longitudinal relaxation time (T1) -weighted image contrast, which is closer to that of commercial Gadovist for magnetic resonance imaging (MRI) applications. This property opens up new avenues in the development of contrast agents.

Balancing the thickness of sensitizing and inert layers in neodymium-sensitized tetralayer nanoconstructs for optimal ultraviolet upconversion and near-infrared cross-linked hydrogel tissue sealants.

Tuning the configuration of lanthanide-doped upconversion nanoparticles (UCNPs) has been proven to be an effective approach to enhance upconversion (UC) efficiency, especially for neodymium (Nd3+)-sensitized UCNPs. Rational configuration design can spatially separate activators and sensitizers, achieving the evolution from single core to multilayer structures. However, optimizing multiphoton UC emission via configuration modulation, especially in the ultraviolet range, is yet to be fully investigated. In this work, thickness tuning of the sensitizing layer containing Nd3+ ions and the inert layer containing gadolinium ions at a fixed combined thickness of 5 nm in tetralayer UCNPs to exclude the size effect is reported for the first time. The optimal thickness of sensitizing and inert layers was determined to be 3 and 2 nm respectively, showing a new strategy of balancing sensitization and surface passivation to enhance 4-photon (360 nm) emission. Although 3-photon emission (475 nm) is mainly influenced by the overall size, its emission intensity remains similar in all the tetralayer UCNPs. Additionally, an 808 nm cross-linked hydrogel has been demonstrated as a potential near-infrared activated tissue sealant. Our results have uncovered the structural parameters for optimal ultraviolet UC emissions and elucidated the strategic importance of nano-configuration design to minimize the energy loss in the high-photon UC process.

Application of Click-chemistry-based perphenylcarbamated beta-CD chiral stationary phase in CEC.

A novel chiral stationary phase (CSP) was prepared by anchoring mono-6-azido-6-deoxyperphenylcarbamated beta-CD onto omega-alkynyl functionalized silica (5 microm) via organic soluble Cu(I)-catalyzed Click chemistry. The obtained CSP was thereafter packed into fused-silica capillary (100 microm id) with an effective length of 9 cm and tested in aqueous CEC to separate a series of racemic aryl alcohols. High separation factors with good resolution were achieved using the current novel CSP. Some pharmaceutical compounds could also be well resolved on this newly derived CSP. The analytical results demonstrate that Click-chemistry-based perphenylcarbamated CSP affords high stability in high electric field and depicts excellent enantioseparation in CEC. The effects of pH value, buffer concentration, applied voltage, concentration of organic modifier and analyte structure on the enantioseparation are also discussed.

Synthesis and application of a novel single-isomer mono-6-deoxy-6-(3R,4R-dihydroxypyrrolidine)-beta-cyclodextrin chloride as a chiral selector in capillary electrophoresis.

A novel positively charged single-isomer of beta-cyclodextrin, mono-6-deoxy-6-(3R,4R-dihydroxypyrrolidine)-beta-CD chloride (dhypy-CDCl), was synthesized and employed as a chiral selector for the first time in capillary electrophoresis (CE) for the enantioseparation of anionic and ampholytic acids. The effects of the running buffer pH, chiral selector concentration, analyte structure and organic modifier on the enantioseparation were studied in detail. The chiral selectivity and resolution for most of the studied analytes decreased as the buffer pH increased in the range of 6.0-9.0. Increasing selector concentration led to decreased effective mobility, increased chiral selectivity and resolution for most of the studied analytes. Moreover, the hydroxyl groups located on the dihydroxypyrrolidine substituent of the dhypy-CDCl could have influence on the chiral separation.

An Upconversion Nanoparticle Enables Near Infrared-Optogenetic Manipulation of the Caenorhabditis elegans Motor Circuit.

Near-infrared (NIR) light penetrates tissue deeply, but its application to motor behavior stimulation has been limited by the lack of known genetic NIR light-responsive sensors. We designed and synthesized a Yb3+/Er3+/Ca2+-based lanthanide-doped upconversion nanoparticle (UCNP) that effectively converts 808 nm NIR light to green light emission. This UCNP is compatible with Chrimson, a cation channel activated by green light; as such, it can be used in the optogenetic manipulation of the motor behaviors of Caenorhabditis elegans. We show that this UCNP effectively activates Chrimson-expressing, inhibitory GABAergic motor neurons, leading to reduced action potential firing in the body wall muscle and resulting in locomotion inhibition. The UCNP also activates the excitatory glutamatergic DVC interneuron, leading to potentiated muscle action potential bursts and active reversal locomotion. Moreover, this UCNP exhibits negligible toxicity in neural development, growth, and reproduction, and the NIR energy required to elicit these behavioral and physiological responses does not activate the animal's temperature response. This study shows that UCNP provides a useful integrated optogenetic toolset, which may have wide applications in other experimental systems.

Ultrasmall-Superbright Neodymium-Upconversion Nanoparticles via Energy Migration Manipulation and Lattice Modification: 808 nm-Activated Drug Release.

Nd3+-sensitized upconversion nanoparticles are among the most promising emerging fluorescent nanotransducers. They are activated by 808 nm irradiation, which features merits such as limited tissue overheating and deeper penetration depth, and hence are attractive for diagnostic and therapeutic applications. Recent studies indicate that ultrasmall nanoparticles (<10 nm) are potentially more suitable for clinical application due to their favorable biodistribution and safety profiles. However, upconversion nanoparticles in the sub-10 nm range suffer from poor luminescence due to their ultrasmall size and greater proportion of lattice defects. To reconcile these opposing traits, we adopt a combinatorial strategy of energy migration manipulation and crystal lattice modification, creating ultrasmall-superbright Nd3+-sensitized nanoparticles with 2 orders of magnitude enhancement in upconversion luminescence. Specifically, we configure a sandwich-type nanostructure with a Yb3+-enriched intermediate layer [Nd3+]-[Yb3+-Yb3+]-[Yb3+-Tm3+] to form a positively reinforced energy migration system, while introducing Ca2+ into the crystal lattice to reduce lattice defects. Furthermore, we apply the nanoparticles to 808 nm light-mediated drug release. The results indicate time-dependent cancer cells killing and better antitumor activities. These ultrasmall-superbright dots have unraveled more opportunities in upconversion photomedicine with the promise of potentially safer and more effective therapy.

Fish scale-derived collagen patch promotes growth of blood and lymphatic vessels in vivo.

In this study, Type I collagen was extracted from fish scales asa potential alternative source of collagen for tissue engineering applications. Since unmodified collagen typically has poor mechanical and degradation stability both in vitro and in vivo, additional methylation modification and 1,4-butanediol diglycidyl ether (BDE) crosslinking steps were used to improve the physicochemical properties of fish scale-derived collagen. Subsequently, in vivo studies using a murine model demonstrated the biocompatibility of the different fish scale-derived collagen patches. In general, favorable integration of the collagen patches to the surrounding tissues, with good infiltration of cells, blood vessels (BVs) and lymphatic vessels (LVs) were observed under growth factor-free conditions. Interestingly, significantly higher (p<0.05) number of LVs was found to be more abundant around collagen patches with methylation modification and BDE crosslinking. Overall, we have demonstrated the potential application of fish scale-derived collagen as a promising scaffolding material for various biomedical applications. STATEMENT OF SIGNIFICANCE: Currently the most common sources of collagen are of bovine and porcine origins, although the industrial use of collagen obtained from non-mammalian species is growing in importance, particularly since they have a lower risk of disease transmission and are not subjected to any cultural or religious constraints. However, unmodified collagen typically has poor mechanical and degradation stability both in vitro and in vivo. Hence, in this study, Type I collagen was successfully extracted from fish scales and chemically modified and crosslinked. In vitro studies showed overall improvement in the physicochemical properties of the material, whilst in vivo implantation studies showed improvements in the growth of blood and lymphatic host vessels in the vicinity of the implants.