Penetration Pathways Research Articles

Study of High Performance Nanoscale Channel Length Vertical Transistors with a Self-Aligned Blocking Layer.

A transistor design employing all vertically stacked components has attracted considerable attention due to the simplicity of the fabrication process and the high conductivity easily realized by achieving nanolevel short channel lengths with two-dimensional current paths. However, fundamental issues, specifically the blocking of the gate electrical field to the semiconductive channel layer and high leakage current at the "off" state, have impeded this configuration in becoming a major transistor design. To address these issues, it has been proposed to introduce a blocking layer (BL) with embedded hole structures and source electrode with embedded hole structures, enhancing gate field penetration and carrier modulation. The hole structure embedded in the source and the BL on the drain induced a desirable combined effect of gate field penetration and carrier pathway modulation. The align accuracy and the hole size difference between BL and source electrode were confirmed as the most important design parameters for high performance of a transistor. We therefore proposed a self-aligning lithography method using a built-in mask that allows high alignment accuracy between the source hole structure and the BL hole structure on the drain over a large area without a high-resolution process system. This method also enables easy and fast fabrication of nanoscale channels with high performance. This design resulted in a transistor with an output of 28 mA/cm2 and an on-off ratio exceeding 106 at 1 mV of VDS. However, at 3 V of VDS, the off-current increased significantly due to short-channel effects in the all metal electrode design. To solve this issue, Fermi level-tunable graphene replaced metal electrodes, maintaining an off-current below 10 pA and an on-off ratio around 107 at 3 V. In addition, the device demonstrates robust electrical properties to light without any special treatment and is stable with a threshold voltage shift of less than 1 V under bias stress. This study demonstrates that the proposed vertical transistor design is a viable candidate as a new major transistor design for various applications.

Analysis of time-of-flight secondary ion mass spectrometry data of human skin treated with diclofenac using sparse autoencoder.

Methods that facilitate molecular identification and imaging are required to evaluate drug penetration into tissues. Time-of-flight secondary ion mass spectrometry (ToF-SIMS), which has high spatial resolution and allows 3D distribution imaging of organic materials, is suitable for this purpose. However, the complexity of ToF-SIMS data, which includes nonlinear factors, makes interpretation challenging. Therefore, in this study, ToF-SIMS data of a stratum corneum treated with diclofenac were analyzed using machine learning to enable the evaluation of drug distribution. Diclofenac-related mass peaks were identified using autoencoder results, and the degree of penetration was evaluated across 2-20th stripped tapes. In addition, the permeation pathway was clarified by comparing the secondary ion images of phosphatidylethanolamine (PhEA; a marker of the inside of the cell); cholesterol, which is abundant in cell membranes; and diclofenac. Based on the biomolecule-related ion images showing the penetration pathway of diclofenac applied to the skin, diclofenac penetrates both the extracellular space and inside cells.

Molecular Insights into the Penetration Enhancement Mechanism of Terpenes to Skin.

Terpenes are widely used in cosmetic formulations as chemical penetration enhancers (CPEs). However, the molecular mechanisms underlying the skin-penetration-enhancing effect have not been completely understood. In this work, molecular dynamics (MD) simulations were used to explore the influence of terpineol (TER), 1,8-cineole (CIN), and limonene (LIM) on the stratum corneum (SC) model. The results indicated that terpenes affected lipid membranes in a concentration-dependent manner and promoted skin permeation by disorganizing the cholesterol (CHOL) portion. The penetration of CPEs across the skin membrane also differed, with diffusion rates of limonene > 1,8-cineole > terpineol. The limonene molecules could penetrate the bilayer's center, forming a "triple layer" membrane structure. Furthermore, constrained simulations showed that the most favorable penetration pathway is via areas rich in CHOL. Terpineol could lower the energy barrier of the hydrophilic molecule (caffeic acid) across the cholesterol region. For the lipophilic molecule (osthole), limonene and 1,8-cineole could reduce the energy barrier across the cholesterol region. Each of the results provides novel insights into the mechanism of penetration of CPEs in the skin.

Durability of new-to-old concrete interface under coupling action of freeze-thaw cycle and chloride salt erosion

This paper investigates two scenarios involving new-to-old concrete: (1) older concrete structures that have undergone freeze-thaw deterioration over time before being repaired, and (2) the integration of new concrete with existing concrete to create a monolithic structure, which is then exposed to freeze-thaw cycling (FTC). The study assesses the durability of these new-to-old concrete specimens, focusing on the combined impacts of FTC and chloride penetration. The anti-freeze-thaw performance is measured through mass changes and ultrasonic testing, while chloride ion penetration is evaluated with Rapid Chloride Migration (RCM) tests. Results show that greater mass loss is observed in new-to-old concrete specimens bonded after freeze-thaw exposure (referred to as FB specimens) compared to those pre-bonded before freeze-thaw exposure (referred to as BF specimens). The reduction in ultrasonic wave velocity is more pronounced in cubic L-BF specimens than in monolithic specimens. The ultrasonic wave velocity of L-BF specimens decreased linearly with an increase in FTC cycles, reaching 30.2 % damage degree at 200 cycles. In cylindrical C-FB specimens, the average migration coefficient of chloride ions in the aged concrete region significantly exceeds that in the new concrete region, with an increase ranging from 58 % to 211 %. However, the difference in the migration coefficient of chloride ions between the aged concrete region and the interface is slight, only slightly lower than that at the interface (−6.54 % to −17.23 %). In C-BF specimens, when the cycle of FTC is less than 50, the average migration coefficient of chloride ions in the new and aged concrete regions is close, with a difference of no more than 7.31 %. As the number of cycles increases, the average migration coefficient of chloride ions in the new concrete region gradually exceeds that in the aged concrete region, with an increase ranging from 29.73 % to 81.84 %. However, they are both substantially lower than the chloride ion diffusion coefficient at interface. The new-to-old concrete interface emerges as the primary pathway for chloride ion penetration. An Interface Zone Effect (IZE) index is introduced, revealing that C-FB specimens with new-to-old concrete bonded after freeze-thaw exposure have lower IZE indices than those of C-BF specimens bonded before freeze-thaw.

New magnetic iron nanoparticle doped with selenium nanoparticles and the mechanisms of their cytoprotective effect on cortical cells under ischemia-like conditions

Ischemic stroke is the cause of high mortality and disability Worldwide. The material costs of stroke treatment and recovery are constantly increasing, making the search for effective and more cost-effective treatment approaches an urgent task for modern biomedicine. In this study, iron nanoparticles doped with selenium nanoparticles, FeNP@SeNPs, which are three-layered structures, were created and characterized using physical methods. Fluorescence microscopy, inhibitor and PCR analyzes were used to determine the signaling pathways involved in the activation of the Ca2+ signaling system of cortical astrocytes and the protection of cells from ischemia-like conditions (oxygen-glucose deprivation and reoxygenation). In particular, when using magnetic selenium nanoparticles together with electromagnetic stimulation, an additional pathway for nanoparticle penetration into the cell is activated through the activation of TRPV4 channels and the mechanism of their endocytosis is facilitated. It has been shown that the use of magnetic selenium nanoparticles together with magnetic stimulation represents an advantage over the use of classical selenium nanoparticles, as the effective concentration of nanoparticles can be reduced many times over.

Boosting OECT Performance with PEGylated Gold Nanoparticles in Hydrophobic Channels

AbstractOrganic electrochemical transistors (OECTs) require organic mixed ion‐electron conductors (OMIECs) (i.e., hydrophilic materials supporting electron and ion transportation) as active materials. However, high‐performance OMIECs grafted with hydrophilic side chains are difficult to synthesize and purify, and often suffer from swelling during operation. In contrast, the synthetic pathways toward a broad range of hydrophobic polymeric semiconductors used in classic organic‐field‐effect transistors are well established, and several are even commercially available. Yet, these hydrophobic materials do not intrinsically support ionic transport, limiting their application in OECTs. Here, poly(ethyleneglycol) (PEG)‐coated gold nanoparticles (AuNP) are incorporated into conventional hydrophobic polymeric semiconductors like poly‐3‐hexylthiophene (P3HT), improving not only ionic but also electronic transport. The hydrophilic AuNPs modify P3HT crystallite orientation, shorten lamellar and π–π distances, and create pathways for ion penetration, as evidenced by GIWAXS and AFM studies. With 5 wt% AuNP loading, OECTs achieve µC* of 98 F cm−1 V−1 s−1, comparable to hydrophilic materials. The strategy also works for other polymer systems, offering a facile method to utilize hydrophobic materials in OECTs and boost their performance.

Single cell combined with laser ablation ICP-MS to study cisplatinum (IV) loaded nanoparticles penetration pathways in osteosarcoma spheroids

Background3D cellular structures have been considered the following step in the evaluation of drugs penetration after 2D cultures since they are more physiologically representative in cancer cell biology. Here the penetration capabilities of Pt (IV)-loaded ultrasmall iron oxide nanoparticles in 143B osteosarcoma multicellular spheroids of different sizes is conducted by a multidimensional quantitative approach. Single cell (SC) and imaging techniques (laser ablation, LA) coupled to inductively coupled plasma-mass spectrometry (ICP-MS) are used to visualize their penetration pathways and distribution in comparison to those of cisplatin. ResultsThe analysis of Pt in disaggregated individual cells from spheroids shows levels of incorporation dependent on the spheroid surface to volume ratio and considerably higher than those observed for cisplatin. These results in combination with the total Pt determination in the complete spheroids reveal a preferential transcellular incorporation pathway of the Pt(IV)-loaded NPs. Elemental imaging by LA-ICP-MS shows the co—localization of Pt/Fe in hot spots at distances up to 100 μm from the spheroid surface reaching concentrations of Pt up to 200 μg g−1 when exposed to Pt(IV)-loaded NPs. A more homogeneous distribution all along the spheroid is observed in the cisplatin-treated models. SignificanceThe multidimensional ICP-MS based analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nano-transported drugs to be applied in the design of nanoparticles with high accumulation at a target site.

Tackling the unyielding: testing two novel approaches against NDM-producing Enterobacterales and Pseudomonas aeruginosa isolates collected in India.

Metallo-β-lactamases are therapeutically challenging due to the limited treatment options. Against such isolates, currently approved newer β-lactam/β-lactamase inhibitor combinations are ineffective. In this study, we tested siderophore cephalosporin, cefiderocol, which utilizes an unconventional iron uptake pathway for efficient cellular penetration, and cefepime/zidebactam that utilizes novel β-lactam enhancer mechanisms for overcoming diverse carbapenemases. Cefiderocol showed limited activity against Escherichia coli isolates co-harboring New Delhi metallo-β-lactamase (NDM) with PBP3 insert, dual carbapenemase (NDM with OXA-48 like)-producing Klebsiella pneumoniae, and NDM-producing Pseudomonas aeruginosa isolates, while cefepime/zidebactam potently inhibited NDM-producing Enterobacterales and P. aeruginosa isolates. NDM being a dominant carbapenemase among Enterobacterales and P. aeruginosa in India, the variable activity of cefiderocol against NDM producers is a concern. Post approval, cefepime/zidebactam could offer a promising treatment option against NDM producers.

Failure analysis of low carbon steel pipeline for district heating and cooling systems: Case studies

In this study, we investigated the failure modes of three low carbon steel pipelines used in district heating and cooling systems. Unlike thermal fatigue and external damage, which are typical causes of pipe failure in district heating and cooling systems, we observed unusual failure cases attributed to corrosion. Microscopic analysis, potentiodynamic polarization tests, and zero resistance ammeter measurements were conducted to analyze the root cause of failure. For the pipe elbow, stress analysis was performed using the finite element method. In the district heating system, fibrous inhomogeneous inclusions accelerated corrosion penetration in the pipeline. For the case of entrapped fibrous ceramic inclusions in pipe (350A), pore clusters formed by the inclusions acted as pathways for corrosion penetration. For the case of entrapped fibrous carbon inclusions in pipe (450A), corrosion penetration of pipeline due to galvanic effects occurred. In the district cooling system, bulging and plastic fracture were observed at the pipe elbow (250A), attributed to the freezing pressure exerted by water on the locally corroded weld joint.

Application of PLGA-PEG-PLGA Nanoparticles to Percutaneous Immunotherapy for Food Allergy.

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies.

Research of the properties of the sandwich-structured Ni60CuMo self-lubricating coating with stepped hardness distribution on Vermicular cast iron by laser cladding

To enhance the wear resistance of Vermicular cast iron (RuT300) and achieve the stepped hardness distribution for the impact deformation resistance in the middle and lower part of the coating and wear resistance in the surface of the coating, the sandwich-structured Ni60CuMo coating with the transition layer was fabricated on RuT300 by laser cladding. The microstructure, hardness, and fracture toughness for the coating were analyzed, and the effect of different loads on wear resistance was investigated. The wear-resistant layer mainly contains Ni-based solid solution, hard phase of chromium compound and some ductile Cu phases. The hardness for coating without cracks shows the stepped distribution, increasing to 381HV0.5, 419HV0.5, and 490HV0.5 in the wear layer, transition layer, and heat-affected zone, respectively. The transition layer can suppress the impact of carbon from the substrate on the hardness of the wear-resistant layer. The wear resistance of the coating demonstrates a self-adaptive enhancement effect with increasing load. As the load increases from 10 N to 30 N and 50 N, the wear rate decreases from 2.865 to 1.525 and 1 (×10⁻⁴mm³N⁻¹m⁻¹). The main wear mechanism is oxidative wear. The extruded ductile Cu phase causes the wear debris to adhere it and the compacted oxide glaze layer is formed with the high load, then the compacted oxide glaze layer isolates oxygen and reduces oxidative wear. In contrast, incomplete oxide layers at low load fail to provide effective isolation, and cracks on the subsurface serve as critical pathways for continued oxygen penetration, resulting in more severe oxidative wear.

Recent Advancements and Trends of Topical Drug Delivery Systems in Psoriasis: A Review and Bibliometric Analysis.

Psoriasis is an immune-mediated inflammatory skin disease where topical therapy is crucial. While various dosage forms have enhanced the efficacy of current treatments, their limited permeability and lack of targeted delivery to the dermis and epidermis remain challenges. We reviewed the evolution of topical therapies for psoriasis and conducted a bibliometric analysis from 1993 to 2023 using a predictive linear regression model. This included a comprehensive statistical and visual evaluation of each model's validity, literature profiles, citation patterns, and collaborations, assessing R variance and mean squared error (MSE). Furthermore, we detailed the structural features and penetration pathways of emerging drug delivery systems for topical treatment, such as lipid-based, polymer-based, metallic nanocarriers, and nanocrystals, highlighting their advantages. This systematic overview indicates that future research should focus on developing novel drug delivery systems characterized by enhanced stability, biocompatibility, and drug-carrying capacity.

Visual detection and tracking of toxic mercury in biological cells using biocompatible mesoporous silica nanospheres

A novel, cost-effective, eco-friendly, and straightforward approach is urgently required to assess the distribution, localization, and concentration of toxins in biological cells, as their accumulation poses significant health risks. Herein, we report innovative fabrication of biocompatible silica nanospheres for real-time tracking, visualization, quantification, and clinical diagnosis of Hg(II) poisoning in cells, employing ultra-sensitive and ultra-selective assays. The creation of a biocompatible yolk-like nanosphere with a highly accessible hollow interior cavity resulted in a distinctive porous structure, providing ultra-precise recognition of Hg(II) at trace levels. The low limits of detection (LOD) and quantification (LOQ) for fluorometric monitoring of Hg(II) ions were determined as 0.11 ppb and 0.33 ppb respectively. Simple, portable, and batch analyses were employed for the rapid and continuous visualization, quantification, and inhibition of ultra-trace Hg(II) concentrations (up to ppb) in HeLa cells, aiming to assess the suitability of the innovative nano- tracker hybrid. The results showed exceptional biocompatibility of the nano-tracker hybrid. The straightforward penetration and binding pathways of the nanospheres through the cell membrane were examined. Moreover, outstanding emission enhancement was observed in the intracellular area under biological conditions. The adorned nanotrackers could serve as valuable tools for visualizing and monitoring Hg(II) poisoning during in vitro assays for clinical diagnosis in HeLa cells.

Autogenous healing of the interface between hollow natural fiber (HNF) and reactive magnesia cement (RMC) matrix

The fiber-matrix interface healing determines the restoration of tensile strength of fiber reinforced cementitious composites (FRCCs). This work first-timely investigates the autogenous healing of debonded interface between hollow natural fiber (HNF) and reactive magnesia cement (RMC) matrix and subsequent tensile strength recovery. HNF-RMC single-fiber specimens are preloaded to induce interfacial debonding, and then conditioned under water-air cycles for healing. The healing-induced recovery of the interfacial properties in the HNF-RMC group are significantly higher than the control PVA-RMC and PVA-PC groups. Tensile test of notched FRCCs demonstrated that the tensile strength of HNF-RMC can be more than doubled after cracking-healing, and its healing efficiency is around 50% higher than that of PVA-PC and PVA-RMC. Based on microstructural characterization in situ and finite element modeling, the increased healing degree is attributed to two new mechanisms related to the special porous microstructure of HNF. First, the lumens and micropores within cell of HNF can be the pathway for CO2 and water penetration, which promotes the formation of healing products (e.g., hydrated magnesium carbonates) within fiber-matrix interface and hence the recovery of chemical and frictional bonds. Second, the healing products formed within lumens caused lateral fiber expansion, and thus prominently enhanced the frictional bond.

High-Resolution Characterization of Enamel Remineralization Using Time-of-Flight Secondary Ion Mass Spectrometry and Electron Microscopy

Introduction: The aim of this in vitro study was to assess the suitability of high-resolution time-of-flight secondary ion mass spectrometry (ToF-SIMS) for visualizing cross-sectional changes in human enamel microstructure and chemical composition during treatment and remineralization cycling of artificially generated caries lesions underneath an artificial plaque. Methods: Treatments consisted of exposure to twice daily toothpaste/water slurries prepared from 0, 1,100, and 5,000 μg/g fluoride (F) NaF/silica toothpastes. In addition, treatments with slurries prepared from 1,100 μg/g F SnF2/silica toothpastes were done using 44Ca in the remineralization solution to allow for differentiation of newly formed mineral and exploration of incorporated metal dopants using ToF-SIMS. Complementary microhardness, scanning electron microscopy, and high-resolution transmission electron microscopy (HR-TEM) investigations were performed on enamel cross sections. Results: HR-TEM was used for the first time to determine the change in crystallinity during remineralization revealing distinct microstructural zones within one lesion. Chemical mapping using ToF-SIMS demonstrated that the distribution of F, while observed primarily in the new mineral phase, was widespread throughout the lesion with 44Ca substantially limited to the remineralizing mineral. Both penetrated the inter-rod spaces of the sound enamel illustrating how acid damage propagates into the native mineral as the caries lesion deepens. HR-TEM examination revealed different regions within the lesion characterized by distinct micro- and ultrastructures. Importantly, HR-TEM revealed a return of crystallinity following remineralization. F dose-response observations verified the ability of these high-resolution techniques to differentiate remineralization efficacy. Conclusion: The collective results provided new insights such as the visualization of F or calcium penetration pathways, as well as new tools to study the caries process.

Long-term stability of lithium–sulfur batteries via synergistic integration of nitrogen-doped graphitic carbon-coated cobalt selenide nanocrystals within porous three-dimensional graphene-carbon nanotube microspheres

Three-dimensional porous microspheres consist of highly conductive reduced graphene oxide-carbon nanotube (rGO‒CNT) framework with well-embedded cobalt selenide (CoSe2) nanocrystals coated with N-doped graphitic carbon (NGC) were synthesized (referred as “P–CoSe2@NGC/rGO‒CNT” microspheres) and utilized as an electrocatalytic interlayer to enhance the performance of lithium-sulfur (Li–S) batteries. The incorporation of the NGC layer and rGO‒CNT framework not only enhances the electronic conductivity significantly but also offers numerous conductive pathways (primary and secondary) for efficient electron transport. Macropores (φ = 100 nm) formed by the decomposition of PS nanobeads (φ = 200 nm) guarantee effective electrolyte penetration and short diffusion pathways. Moreover, the CoSe2 nanocrystals offer a multitude of polar active sites that effectively anchor polysulfide intermediates, reducing the loss of active material. Benefiting from the nanostructure merits, Li–S cells featuring a P–CoSe2@NGC/rGO‒CNT-coated separator and a conventional sulfur electrode demonstrated outstanding rate capability (up to 2.0 C) and remarkable cycling stability (1000 cycles at 2.0 C). Even under more demanding cell conditions, such as high sulfur content (71 %), high sulfur loading (4.6 mg cm−2), and low E/S (5.6 μL mg−1) ratio, the cell exhibits impressive cycling stability with 420 cycles at 0.1 C, along with feasible rate performance up to 0.3 C.

Characterization of nanoscale pinhole defects in hydrophobic coatings using copper electrodeposition

Thin (∼ 100 nm thick) hydrophobic polymer films are used in a plethora of applications where water repellency is required. However, hydrophobic film implementation in industry is limited due to poor durability. Thin hydrophobic film blistering during condensation has been identified as one of the main mechanisms associated with failure. Yet, disagreement exists about the source of blister initiation. Furthermore, there is a lack of understanding about the physical defects or pinholes that facilitate vapor penetration pathways through thin hydrophobic films. These pinholes govern the nucleation of blisters on the interface between the hydrophobic polymer and metal substrate. Here, we use metal electrodeposition as a means to characterize these intrinsic pinholes in thin hydrophobic polymers. A facile method is demonstrated to locate pinholes and measure pinhole density on CFx and poly(2-chloro-p-xylylene) (Parylene C) films. Our work not only helps to understand the intrinsic defects associated with film deposition, it also provides design guidelines for the selection and development of efficient thin film hydrophobic coatings.

Optimization, characterization, and follicular targeting assessment of tretinoin and bicalutamide loaded niosomes

Acne vulgaris, a prevalent skin disorder among teenagers and young adults, can have numerous psychological consequences. Topical treatment of acne would be advantageous by reducing the risk of systemic adverse drug reactions. However, the major challenge would be skin penetration through the stratum corneum. Therefore, during this study, tretinoin (TRT) and bicalutamide (BCT) loaded niosomes with follicular targeting potential were fabricated through the thin film hydration technique. Formulation optimization was performed using the Design-Expert software and optimum formulation was characterized in terms of particle size, zeta potential, transmission electron microscopy, drug loading, and differential scanning calorimetry. In vivo follicular targeting was assessed using rhodamine B-loaded niosomes to follow the skin penetration pathways. The results showed that, the optimum formulation was spherical in shape and had an average diameter of 319.20 ± 18.50 nm and a zeta potential of − 29.70 ± 0.36 mV. Furthermore, entrapment efficiencies were 94.63 ± 0.50% and > 99% and loading capacities were 1.40 ± 0.01% and 1.48 ± 0.00% for BCT and TRT, respectively. According to the animal study results, the prepared niosomes with an average diameter of about 300 nm showed significant accumulation in hair follicles. It seems that the designed niosomal BCT-TRT co-delivery system would be promising in acne management with follicular targeting potential.

Generalised analytical method unravels framework-dependent kinetics of adsorption-induced structural transition in flexible metal–organic frameworks

Flexible metal–organic frameworks (MOFs) exhibiting adsorption-induced structural transition can revolutionise adsorption separation processes, including CO2 separation, which has become increasingly important in recent years. However, the kinetics of this structural transition remains poorly understood despite being crucial to process design. Here, the CO2-induced gate opening of ELM-11 ([Cu(BF4)2(4,4’-bipyridine)2]n) is investigated by time-resolved in situ X-ray powder diffraction, and a theoretical kinetic model of this process is developed to gain atomistic insight into the transition dynamics. The thus-developed model consists of the differential pressure from the gate opening (indicating the ease of structural transition) and reaction model terms (indicating the transition propagation within the crystal). The reaction model of ELM-11 is an autocatalytic reaction with two pathways for CO2 penetration of the framework. Moreover, gas adsorption analyses of two other flexible MOFs with different flexibilities indicate that the kinetics of the adsorption-induced structural transition is highly dependent on framework structure.

Size-Dependent Penetration of Nanoparticles in Tumor Spheroids: A Multidimensional and Quantitative Study of Transcellular and Paracellular Pathways.

Tumor penetration of nanoparticles is crucial in nanomedicine, but the mechanisms of tumor penetration are poorly understood. This work presents a multidimensional, quantitative approach to investigate the tissue penetration behavior of nanoparticles, with focuses on the particle size effect on penetration pathways, in an MDA-MB-231 tumor spheroid model using a combination of spectrometry, microscopy, and synchrotron beamline techniques. Quasi-spherical gold nanoparticles of different sizes are synthesized and incubated with 2D and 3D MDA-MB-231 cells and spheroids with or without an energy-dependent cell uptake inhibitor. The distribution and penetration pathways of nanoparticles in spheroids are visualized and quantified by inductively coupled plasma mass spectrometry, two-photon microscopy, and synchrotron X-ray fluorescence microscopy. The results reveal that 15nm nanoparticles penetrate spheroids mainly through an energy-independent transcellular pathway, while 60nm nanoparticles penetrate primarily through an energy-dependent transcellular pathway. Meanwhile, 22nm nanoparticles penetrate through both transcellular and paracellular pathways and they demonstrate the greatest penetration ability in comparison to other two sizes. The multidimensional analytical methodology developed through this work offers a generalizable approach to quantitatively study the tissue penetration of nanoparticles, and the results provide important insights into the designs of nanoparticles with high accumulation at a target site.