Core Multishell Research Articles

Topical Application of Dexamethasone-Loaded Core-Multishell Nanocarriers Against Oral Mucosal Inflammation.

Topical treatment of oral inflammatory diseases is challenging due to the intrinsic physicochemical barriers of the mucosa and the continuous flow of saliva, which dilute drugs and limit their bioavailability. Nanocarrier technology can be an innovative approach to circumvent these problems and thus improve the efficacy of topical drug delivery to the mucosa. Core-multishell (CMS) nanocarriers are putative delivery systems with high biocompatibility and the ability to adhere to and penetrate the oral mucosa. Ester-based CMS nanocarriers release the anti-inflammatory compound dexamethasone (Dx) more efficiently than a conventional cream. Mussel-inspired functionalization of a CMS nanocarrier with catechol further improves the adhesion of the nanocarrier and may enhance the efficacy of the loaded drugs. In the present study, the properties of the ester-based CMS 10-E-15-350 nanocarrier (CMS-NC) are further evaluated in comparison to the catechol-functionalized variant (CMS-C0.08). While the mucoadhesion of CMS-NC is inhibited by saliva, CMS-C0.08 exhibits better mucoadhesion in the presence of saliva. Due to the improved adhesion properties, CMS-C0.08 loaded with dexamethasone (Dx-CMS-C0.08) shows a better anti-inflammatory effect than Dx-CMS-NC when applied dynamically. These results highlight the superiority of CMS-C0.08 over CMS-NC as an innovative drug delivery system (DDS) for the treatment of oral mucosal diseases.

Exploring energy mechanisms involved in the luminescence reduction due to Ce3+ doping via core-multishell upconversion nanoparticles highly doped with Ho3+ and Yb3+

Upconversion nanoparticles (UCNPs), particularly those that are highly doped, possess outstanding properties and have demonstrated tremendous application potential. However, novel fine-tuning strategies are urgently required to enhance the upconversion luminescence (UCL) performance of UCNPs. In this study, a series of core–multishell UCNPs highly doped with Ho3+ and Yb3+ ions were synthesized via the oleate route. The X-ray diffraction (XRD), transmission electron microscopy (TEM), and UCL spectra and decay times, and pump power dependency of the synthesized UCNPs were used to examine their morphology, size, and the UCL properties. Ce3+ ions were introduced to enhance Ho3+-based red UCL, and their doping strategy was also optimized based on summarized UCL trends and detailed UCL mechanism analysis. NaHoF4:Gd3+@NaGdF4:Yb3+,Ce3+@NaGdF4:Yb3+ UCNPs that had 10 mol% Ce3+ dopants in their middle shells exhibited better UCL properties than the larger traditional NaGdF4:Yb3+,Ce3+,Ho3+ UCNPs, probably because of the combined influence of the energy interactions between the Ce3+ ions and surface groups, sensitizing energy enhancement by active shells, and the positive cooperation between the Ce3+ ions and highly-doped core–shell structures. In this study, the phenomenon of UCL decrease resulting from Ce3+ ion doping was explored. Using unique core–multishell structures with highly-doped activators and sensitizers placed within and outside the structures, respectively, the UCL decrease due to Ce3+ ion doping was attributed to a competition for photons. Doping the UCNPs with Ce3+ ions near the UCNP surfaces favors Ho3+-based red UCL. Our study findings can deepen the understanding of the Ho3+-based UCL mechanisms and increase the potential uses of NaHoF4 materials in photo-induced therapy.

Simultaneous 980 and 800 nm Orthogonal Upconversion and Ligand-Sensitized Downshifting of Triply Excited and Multicolor-Emitted Core–Multishell Nanocrystals for High-Level Anticounterfeiting Applications

Simultaneous 980 and 800 nm Orthogonal Upconversion and Ligand-Sensitized Downshifting of Triply Excited and Multicolor-Emitted Core–Multishell Nanocrystals for High-Level Anticounterfeiting Applications

Enhanced Light Extraction of Nano‐Light‐Emitting Diodes with Metal‐Clad Structure Using Vertical GaAs/GaAsP Core–Multishell Nanowires on Si Platform

Enhanced Light Extraction of Nano‐Light‐Emitting Diodes with Metal‐Clad Structure Using Vertical GaAs/GaAsP Core–Multishell Nanowires on Si Platform

Enhanced Light Extraction of Nano‐Light‐Emitting Diodes with Metal‐Clad Structure Using Vertical GaAs/GaAsP Core–Multishell Nanowires on Si Platform

Nanometer‐scaled light sources using III–V compound semiconductor nanowires (NWs) on Si are expected as building blocks for next‐generation Si photonics, bioimaging, on‐chip microscopy, and light detection and ranging (LiDAR) techniques. This is, however, limited in a few materials systems due to complexity in integration of the vertical III–V NWs on Si and device process flow. Suppressing optical loss in the NW materials beyond the optical diffraction remains difficult in enhancing light extraction. Herein, the effect of the vertical metal‐clad architectures for the vertical nano‐light‐emitting diodes (LEDs) using GaAs/GaAsP‐related core–multishell NWs heterogeneously integrated on Si is investigated. The grown core–multishell NW is composed of a radial n‐GaAs/n‐GaAsP/p‐GaAs/p‐GaAsP double heterostructure. The vertical metal‐clad NW‐LEDs show suppression of carrier overflow effect and rapid enhancement of electrical luminescence.

Efficacy of topically applied rapamycin-loaded redox-sensitive nanocarriers in a human skin/T cell co-culture model.

Rapamycin, also known as Sirolimus, is a promising anti-proliferative drug, but its therapeutic use for the topical treatment of inflammatory, hyperproliferative skin disorders is limited by insufficient penetration rates due to its high molecular weight (MW of 914.172g/mol) and high lipophilicity. We have shown that core multi-shell (CMS) nanocarriers sensitive to oxidative environment can improve drug delivery to the skin. In this study, we investigated the mTOR inhibitory activity of these oxidation-sensitive CMS (osCMS) nanocarrier formulations in an inflammatory ex vivo human skin model. In this model, features of inflamed skin were introduced by treating the ex vivo tissue with low-dose serine protease (SP) and lipopolysaccharide (LPS), while phorbol 12-myristate 13-acetate and ionomycin were used to stimulate IL-17A production in the co-cultured SeAx cells. Furthermore, we tried to elucidate the effects of rapamycin on single cell populations isolated from skin (keratinocytes, fibroblast) as well as on SeAx cells. Further, we measured possible effects of the rapamycin formulations on dendritic cell (DC) migration and activation. The inflammatory skin model enabled the assessment of biological readouts at both the tissue and T cell level. All investigated formulations successfully delivered rapamycin across the skin as revealed by reduced IL-17A levels. Nevertheless, only the osCMS formulations reached higher anti-inflammatory effects in the skin compared to the control formulations with a significant downregulation of mTOR activity. These results indicate that osCMS formulations could help to establish rapamycin, or even other drugs with similar physico-chemical properties, in topical anti-inflammatory therapy.

Nonblinking Core–Multishell InP/ZnSe/ZnS Quantum Dot Bioconjugates for Super-resolution Imaging

Colloidal quantum dots (QDs) are vital fluorescent probes with several optical features superior to those found in organic dyes for microscopy imaging. However, the emission blinking behavior of a single QD is an intrinsic drawback for stimulated emission depletion microscopy (STED) or structured illumination microscopy techniques. Herein, we present a rational strategy for the synthesis of a type of deterministic, environmentally friendly, small nonblinking core–multishell InP/ZnSe/ZnS QD using a hydrofluoric acid (HF) etching passivation. The strategy includes four steps: synthesis of the InP core, synthesis of oil-phase core–multishell InP/ZnSe/ZnS QDs using hydrogen fluoride and trioctylphosphine etching passivation, promotion of the water solubility of QDs modified by 3-mercaptopropionic acid (MPA), and enhanced biotargeting of core–multishell InP/ZnSe/ZnS QDs by surface coupling technology. The suppressed blinking mechanism was primarily attributed to surface wrapping shells and HF etching passivation of surface dangling bonds, which reduced surface nonradiative recombination. Nonblinking QDs exhibit high fluorescence efficiency (∼90%), good photostability (>20 min), a large Stokes shift (>135 nm), biocompatibility of the cell viability (>90%), and high targeting. Furthermore, super-resolution multifocal structured illumination microscopy imaging of subcellular structures labeled using these QDs confirmed a resolution improvement of greater than 2.6-fold compared to wide-field microscopy. The results indicate that the nonblinking QDs can function as excellent probes for use in the long-term super-resolution visualization of subcellular dynamics.

Cascaded Photon Confinement‐Mediated Orthogonal RGB‐Switchable NaErF4‐Cored Upconversion Nanoarchitectures for Logicalized Information Encryption and Multimodal Luminescent Anti‐Counterfeiting

AbstractOrthogonal upconversion nanoparticles (UCNPs) have received increasing research attention due to their unique optical performance. However, the establishment of the orthogonal UCNPs emitting primary red/green/blue (RGB) UCL remains a great challenge. Herein, RGB‐switchable NaErF4‐cored core–multishell UCNPs (RGB‐UCNPs) are constructed through the coordinative implementation of outside‐in cascaded photon harvesting and interfacial energy‐transfer (IET) inhibition. By modulating several constructional factors, the power‐density‐independent red, green, and blue luminescence in high color purity is readily available in the elaborated RGB‐UCNPs under 1550, 808, and 980 nm excitations, respectively. Notably, full‐color emissions, involving red, yellow, green, cyan, blue, magenta and white, are dynamically implemented in this single architecture through manipulating the excitation power of the combined 1550/808/980 nm lasers. These emission profiles of RGB‐UCNPs make them promising in broad photonic applications. As a proof of concept, the viability of the logicalized information encryption strategy and smartphone APP‐assisted multimodal luminescent QR code anti‐counterfeiting technique is demonstrated, which are both established based on directly useable RGB‐UCNPs with assistance of a self‐built combined laser system. This work not only opens up a new avenue to gain RGB‐switchable UCL and flexible full‐color output in a single nanostructure, but also provides enlightenment for developing the application scenarios of multicolor‐tunable UCNPs.

Design of core-multi shell flame retardant towards fire safe thermoplastic polyurethane composites with low toxic fumes generation

Superior flame retardancy and excellent smoke suppression are two significant issues in thermoplastics, especially for thermoplastic polyurethane (TPU) with extensive application in industrial fields. It is of great significance, but hardly achievable, to simultaneously impart these properties to TPU. Herein, we reported the titanium carbide and coupling agent functionalized the silicon-wrapped ammonium polyphosphate (NSiAPP@Ti3C2Tx) via hydrogen-bonding interaction and microencapsulation, which were then adopted to enhance the fire safety of TPU. The as-prepared TPU/9.0NSiAPP@1.0Ti3C2Tx composite showed the V-0 rating in the UL-94 testing and its LOI value was increased to 27.6%. Besides, the cone calorimetry results indicated that the peak of heat release rate, total smoke release, total carbon monoxide yield and total carbon dioxide yield of the TPU/9.0NSiAPP@1.0Ti3C2Tx were significantly decreased by 78.1%, 72.6%, 53.7% and 67.5%, respectively, as compared to those of pure TPU. The outstanding charring effect and excellent barrier function together with the prominent terminating action of the NSiAPP@Ti3C2Tx hybrid caused the remarkable enhancement of the fire resistance for TPU composites. This work offers a promising strategy for endowing TPU composite with high flame retardancy and superior smoke suppression.

Novel Adhesive Nanocarriers Based on Mussel-Inspired Polyglycerols for the Application onto Mucosal Tissues

A synthetic route for adhesive core-multishell (CMS) nanocarriers for application to the oral mucosa was established using mussel-inspired catechol moieties. The three CMS nanocarriers with 8%, 13%, and 20% catechol functionalization were evaluated for loading capacity using Nile red, showing an overall loading of 1 wt%. The ability of Nile red loaded and functionalized nanocarriers to bind to a moist mucosal surface was tested in two complementary adhesion assays under static and dynamic conditions using monolayers of differentiated gingival keratinocytes. Adhesion properties of functionalized nanocarriers were compared to the adhesion of the non-functionalized nanocarrier. In both assays, the CMS nanocarrier functionalized with 8% catechol exhibited the strongest adhesion compared to its catechol-free counterpart and the CMS nanocarriers functionalized with 13% and 20% catechol.

Preclinical Testing of Dendritic Core-Multishell Nanoparticles in Inflammatory Skin Equivalents.

Human skin equivalents emerged as novel tools in preclinical dermatological research. It is being claimed that they may bridge the translational gap between preclinical and clinical research, yet only a few studies have investigated their suitability for preclinical drug testing so far. Therefore, we investigated if inflammatory skin equivalents, which emulate hallmarks of atopic dermatitis (AD), are suitable to assess the anti-inflammatory effects of dexamethasone (DXM) in a cream formulation or loaded onto dendritic core-multishell nanoparticles. Topical DXM application resulted in significantly decreased expression of the proinflammatory cytokine TSLP, increased expression of the skin barrier protein involucrin, and facilitated glucocorticoid receptor translocation in a dose-dependent manner. Further, DXM treatment inhibited gene expression of extracellular matrix components, potentially indicative of the known skin atrophy-inducing side effects of glucocorticoids. Overall, we were able to successfully assess the anti-inflammatory effects of DXM and the superiority of the nanoparticle formulation. Nevertheless the identification of robust readout parameters proved challenging and requires careful study design.

Synergic effect of Te, Ni and MWCNT on creep behavior and microstructural evolution of Sn-1.0Ag-0.7Cu low-Ag solder

Avoiding the weak interface bonding of multi-walled carbon nanotubes MWCNT with Sn-Ag-Cu solder matrix is vital to produce high performance large scale Sn-Ag-Cu solder alloys. In this work, Sn-1.0Ag-0.7Cu (SAC107) composite solders were developed by incorporating MWCNT in SAC107 alloy with Ni and Te. The results indicate that the MWCNTs and Cu can be instantaneously adsorbed at the surface-active of Te atoms to in situ compose the core multi-shell (Te/C/Cu/C) polygonal particles, linking MWCNT with SAC solder matrix. The polygonal particles are well dispersed through the Cu6Sn5, Ag3Sn, β-Sn, SnTe and (Cu,Ni)6Sn5 IMC precipitates. These structural variations produce a combination of increased creep resistance 15 times and enlarged creep life time (14 times) than that of plain SAC107 alloy. Although Ni and Te additions decreased the creep resistance of SAC, the SAC-Ni-Te-MWCNT composite alloy exhibits significant change in dislocation creep resistance with creep stress exponent of ~ 6.6 at 25 °C: the creep threshold stress is decreased by 58.8% (5 MPa) in SAC-Ni-Te alloy, while increased by 17.6% (1.5 MPa) in SAC-Ni-Te-MWCNT composite alloy owing to the presence of polygonal particles.

Molecular beam epitaxial growth of GaAs/GaNAsBi core–multishell nanowires

GaAs/GaNAsBi/GaAs core–multishell nanowires were grown using molecular beam epitaxy on Si(111) substrates. The formation of the 20 nm wide GaNAsBi shell with a regular hexagonal structure was observed. The shell is estimated to contain approximately 1.5% N and 2.6% Bi and has a compressive lattice mismatch of less than 0.2% with GaAs layers. The strain mediation by the introduction of both N and Bi suppresses the crystalline deformation, resulting in the clear formation of the GaNAsBi shell. Thus, we obtained room-temperature photoluminescence with the maximum position at approximately 1300 nm from the GaAs/GaNAsBi/GaAs core–multishell nanowires.

Topical Delivery of Rapamycin by Means of Microenvironment-Sensitive Core-Multi-Shell Nanocarriers: Assessment of Anti-Inflammatory Activity in an ex vivo Skin/T Cell Co-Culture Model.

IntroductionRapamycin (Rapa) is an immunosuppressive macrolide that inhibits the mechanistic target of rapamycin (mTOR) activity. Thanks to its anti-proliferative effects towards different cell types, including keratinocytes and T cells, Rapa shows promise in the treatment of skin diseases characterized by cell hyperproliferation. However, Rapa skin penetration is limited due to its lipophilic nature (log P = 4.3) and high molecular weight (MW = 914 g/mol). In previous studies, new microenvironment-sensitive core multishell (CMS) nanocarriers capable of sensing the redox state of inflamed skin were developed as more efficient and selective vehicles for macrolide delivery to inflamed skin.MethodsIn this study, we tested such redox-sensitive CMS nanocarriers using an inflammatory skin model based on human skin explants co-cultured with Jurkat T cells. Serine protease (SP) was applied on skin surface to induce skin barrier impairment and oxidative stress, whereas phytohaemagglutinin (PHA), IL-17A, and IL-22 were used to activate Jurkat cells. Activation markers, such as CD45 and CD69, phosphorylated ribosomal protein S6 (pRP-S6), and IL-2 release were monitored in activated T cells, whereas pro-inflammatory cytokines were measured in skin extracts and culture medium.ResultsWe found that alteration of skin barrier proteins corneodesmosin (CDSN), occludin (Occl), and zonula occludens-1 (ZO-1) as well as oxidation-induced decrease of free thiol groups occurred upon SP-treatment. All Rapa formulations exerted inhibitory effects on T cells after penetration across ex vivo skin. No effects on skin inflammatory markers were detected. The superiority of the oxidative-sensitive CMS nanocarriers over the other formulations was observed with regard to drug delivery as well as downregulation of IL-2 release.ConclusionOverall, our results demonstrate that nanocarriers addressing features of diseased skin are promising approaches to improve the topical delivery of macrolide drugs.

Robust Electrodes for Flexible Energy Storage Devices Based on Bimetallic Encapsulated Core-Multishell Structures.

Developing flexible electrodes with high active materials loading and excellent mechanical stability is of importance to flexible electronics, yet remains challenging. Herein, robust flexible electrodes with an encapsulated core‐multishell structure are developed via a spraying‐hydrothermal process. The multilayer electrode possesses an architecture of substrate/reduced graphene oxide (rGO)/bimetallic complex/rGO/bimetallic complex/rGO from the inside to the outside, where the cellulosic fibers serve as the substrate, namely, the core; and the multiple layers of rGO and bimetallic complex, are used as active materials, namely, the shells. The inner two rGO interlayers function as the cement that chemically bind to two adjacent layers, while the two outer rGO layers encapsulate the inside structure effectively protecting the electrode from materials detachment or electrolyte corrosion. The electrodes with a unique core‐multishell structure exhibit excellent cycle stability and exceptional temperature tolerance (−25 to 40 °C) for lithium and sodium storage. A combination of experimental and theoretical investigations are carried out to gain insights into the synergetic effects of cobalt‐molybdenum‐sulfide (CMS) materials (the bimetallic complex), which will provide guidance for future exploration of bimetallic sulfides. This strategy is further demonstrated in other substrates, showing general applicability and great potential in the development of flexible energy storage devices.

Importance of Surface Functionalization and Purification for Narrow FWHM and Bright Green-Emitting InP Core–Multishell Quantum Dots via a Two-Step Growth Process

Importance of Surface Functionalization and Purification for Narrow FWHM and Bright Green-Emitting InP Core–Multishell Quantum Dots via a Two-Step Growth Process

Core–Multishell Cathode Materials: Core–Multishell‐Structured Digital‐Gradient Cathode Materials with Enhanced Mechanical and Electrochemical Durability (Small 19/2021)

Core–Multishell Cathode Materials: Core–Multishell‐Structured Digital‐Gradient Cathode Materials with Enhanced Mechanical and Electrochemical Durability (Small 19/2021)

Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa

ObjectivesTopical drug administration is commonly applied to control oral inflammation. However, it requires sufficient drug adherence and a high degree of bioavailability. Here, we tested the hypothesis whether an ester-based core-multishell (CMS) nanocarrier is a suitable nontoxic drug-delivery system that penetrates efficiently to oral mucosal tissues, and thereby, increase the bioavailability of topically applied drugs.Material and methodsTo evaluate adhesion and penetration, the fluorescence-labeled CMS 10-E-15-350 nanocarrier was applied to ex vivo porcine masticatory and lining mucosa in a Franz cell diffusion assay and to an in vitro 3D model. In gingival epithelial cells, potential cytotoxicity and proliferative effects of the nanocarrier were determined by MTT and sulphorhodamine B assays, respectively. Transepithelial electrical resistance (TEER) was measured in presence and absence of CMS 10-E-15-350 using an Endohm-12 chamber and a volt-ohm-meter. Cellular nanocarrier uptake was analyzed by laser scanning microscopy. Inflammatory responses were determined by monitoring pro-inflammatory cytokines using real-time PCR and ELISA.ResultsCMS nanocarrier adhered to mucosal tissues within 5 min in an in vitro model and in ex vivo porcine tissues. The CMS nanocarrier exhibited no cytotoxic effects and induced no inflammatory responses. Furthermore, the physical barrier expressed by the TEER remained unaffected by the nanocarrier.ConclusionsCMS 10-E-15-350 adhered to the oral mucosa and adhesion increased over time which is a prerequisite for an efficient drug release. Since TEER is unaffected, CMS nanocarrier may enter the oral mucosa transcellularly.Clinical relevanceNanocarrier technology is a novel and innovative approach for efficient topical drug delivery at the oral mucosa.

Core-Multishell-Structured Digital-Gradient Cathode Materials with Enhanced Mechanical and Electrochemical Durability.

Ni-rich cathode materials provide high energy density, but their structural and surface instability limits their cyclability and thermal stability. As one of the approaches to mitigate this problem, cathode materials comprising Ni-rich high-capacity core wrapped in Mn-rich multiple shells are produced successfully. In contrast to the conventional batch-type process for concentration-gradient materials, a digital-gradient cascade coprecipitation process described here achieves the improvements in productivity and quality consistency needed to move toward large-scale manufacturing. The core-multishell cathode materials produced in this manner not only have longer cycle life and improved rate performance compared to homogeneous Ni-rich cathode materials having the same overall composition, but also show remarkably enhanced thermal stability and low impedance growth characteristics. In a novel attempt to determine the correlation between the mechanical properties of the core-multishell cathode particles and their electrochemical cyclabilities, their breaking force and elasticity were successfully measured using a statistical approach, which indicates that a cathode particle with stable surface composition as well as high breaking force has improved capacity retention and durability. These results guide the realization of long life and high thermal stability in Ni-rich cathode materials through heterogeneous particle engineering.

Redox-Responsive Nanocarrier for Controlled Release of Drugs in Inflammatory Skin Diseases.

A synthetic route for redox-sensitive and non-sensitive core multi-shell (CMS) carriers with sizes below 20 nm and narrow molecular weight distributions was established. Cyclic voltammetric measurements were conducted characterizing the redox potentials of reduction-sensitive CMS while showcasing its reducibility through glutathione and tris(2-carboxyethyl)-phosphine as a proof of concept. Measurements of reduction-initiated release of the model dye Nile red by time-dependent fluorescence spectroscopy showed a pronounced release for the redox-sensitive CMS nanocarrier (up to 90% within 24 h) while the non-sensitive nanocarriers showed no release in PBS. Penetration experiments using ex vivo human skin showed that the redox-sensitive CMS nanocarrier could deliver higher percentages of the loaded macrocyclic dye meso-tetra (m-hydroxyphenyl) porphyrin (mTHPP) to the skin as compared to the non-sensitive CMS nanocarrier. Encapsulation experiments showed that these CMS nanocarriers can encapsulate dyes or drugs with different molecular weights and hydrophobicity. A drug content of 1 to 6 wt% was achieved for the anti-inflammatory drugs dexamethasone and rapamycin as well as fluorescent dyes such as Nile red and porphyrins. These results show that redox-initiated drug release is a promising strategy to improve the topical drug delivery of macrolide drugs.