Silica Microparticles Research Articles

Quantifying aquifer heterogeneity using superparamagnetic DNA particles

Identifying and determining hydraulic parameters of physically heterogeneous aquifers is pivotal for flow field analysis, contaminant migration and risk assessment. In this research, we applied a novel uniquely sequenced DNA tagged superparamagnetic silica microparticles (SiDNAmag) to quantify hydraulic parameters and associated uncertainties of a heterogeneous sand tank. In the sand tank with lens shaped heterogeneity, we conducted three sets of multi – point injection experiments in unconsolidated (1) homogeneous (zone 0), (2) heterogeneous with a no-conductivity-zone (zone 1), and (3) heterogeneous with a high-conductive-zone (zone 2). From the breakthrough curves (BTC), we estimated the parameters distributions of hydraulic conductivity (k), effective porosity (ne), longitudinal dispersivity (αL), transverse vertical (αTV), and transverse horizontal dispersivities (αTH) applying Monte Carlo simulation approach for BTC fitting. The estimated parameters and associated uncertainties for each of the heterogeneous sections were further statistically compared (distribution non-specific Mann Whitney U test) these parameter distributions with parameter distributions estimated from the conservative salt tracer. While the time of arrival and time to peak concentration of SiDNAmag and salt in effluent were comparable, peak concentration of SiDNAmag was 1–3 log reduced as compared to the salt tracer due to first order kinetic attachment. Nonetheless, the parameters and associated uncertainty distributions (5 %–95 %) of K, ne, αL, αTV, and αTH, determined from SiDNAmag BTCs were statistically equivalent to the salt tracer in all three experiment systems. Through our experimental and modelling approach, our work demonstrated that in a coarse to very coarse grain sand medium, with lens shaped heterogeneity, the uniquely sequenced SiDNAmag were a promising tool to identify heterogeneity and determine hydraulic parameters and associated uncertainty distributions.

Three-Dimensional (3D) Surface-Enhanced Raman Spectroscopy (SERS) Substrates for Sensing Low-Concentration Molecules in Solution

The use of surface-enhanced Raman spectroscopy (SERS) in liquid solutions has always been challenging due to signal fluctuations, inconsistent data, and difficulties in obtaining reliable results, especially at very low analyte concentrations. In our study, we introduce a new method using a three-dimensional (3D) SERS substrate made of silica microparticles (SMPs) with attached plasmonic nanoparticles (NPs). These SMPs were placed in low-concentration analyte solutions for SERS analysis. In the first approach to perform SERS in a 3D environment, glycerin was used to immobilize the particles, which enabled high-resolution SERS imaging. Additionally, we conducted time-dependent SERS measurements in an aqueous solution, where freely suspended SMPs passed through the laser focus. In both scenarios, EFs larger than 200 were achieved, which enabled the detection of low-abundance analytes. Our study demonstrates a reliable and reproducible method for performing SERS in liquid environments, offering significant advantages for the real-time analysis of dynamic processes, sensitive detection of low-concentration molecules, and potential applications in biomolecular interaction studies, environmental monitoring, and biomedical diagnostics.

Impact of Surface Chemistry and Particle Size on Inertial Cavitation Driven Transport of Silica Nanoparticles and Microparticles

AbstractThis study investigated the high‐intensity focused ultrasound (HIFU)‐mediated propulsion of mesoporous silica nanoparticles (MSNs) and microspheres (MSMs). Nanoparticles are heavily sought as vehicles for drug delivery, but their transport through tissue is often restricted. Here, MSNs and MSMs are hydrophobically modified and coated with phospholipids to facilitate inertial cavitation to promote propulsion under HIFU. Modified nanoparticles show significantly enhanced cavitation and propulsion, achieving a maximum displacement of 250 µm (≈2500 body length) and speed of ≈1600 µm s−1 (16 000 body length s−1), compared to unmodified nanoparticles (2 µm, 20 body length, 60 µm s−1, 600 body length). In contrast, microparticles demonstrate comparable cavitation responses. Modified microparticles reached a maximum speed of 4000 µm s−1 (800 body length s−1) and displacement of 230 µm (46 body length), and unmodified microparticles achieved 2000 µm s−1 (400 body length s−1) and 75 µm (15 body length). In all HIFU‐responsive samples, displacement and speed decreased with successive pulses, implying that particles fatigue with continued pulsing. Analyses of particle trajectories and rotational diffusion times suggest that cavitation occurs uniformly on particle surfaces rather than at specific sites. These principles are important for the design of future drug‐delivery vehicles capable of ultrasound‐triggered motion.

Butterflies and bifurcations in surface radio-frequency traps: The diversity of routes to chaos.

In the present article, we investigate the charged micro-particle dynamics in the surface radio-frequency trap (SRFT). We have developed a new configuration of the SRFT that consists of three curved electrodes on a glass substrate for massive micro-particles trapping. We provide the results of numerical simulations for the dynamical regimes of charged silica micro-particles in the SRFT. Here, we introduce a term of a "main route" to chaos, i.e., the sequence of dynamical regimes for the given particles with the increase of the strength of an electric field. Using the Lyapunov exponent formalism, typical Reynolds number map, Poincaré sections, bifurcation diagrams, and attractor basin boundaries, we have classified three typical main routes to chaos depending on the particle size. Interestingly, in the system described here, all main scenarios of a transition to chaos are implemented, including the Feigenbaum scenario, the Landau-Ruelle-Takens-Newhouse scenario as well as intermittency.

Parallel Concentric Wrinkled Polydimethylsiloxane Patterns and Their Potential Biomedical Applications

AbstractThe objective of this study is to examine microbial behavior by fabricating and applying parallel concentric wrinkled patterns to polydimethylsiloxane (PDMS) substrates. The patterns are generated and subsequently relaxed in a rigid silica layer, resulting in the formation of discernible wrinkles that can be analyzed using electron microscopy and light diffraction. The alignment of E. coli and silica microparticles is facilitated by these structures along the creases. Within these creases, E. coli exhibits enhanced attachment and rotational mobility in regions characterized by hydrophobic cracks. Furthermore, the bacteria demonstrate an increase in velocity when propelled by the PDMS creases, suggesting that these structures are capable of guiding microbial motion. In addition, distinct alignment and growth patterns are observed for E. coli proliferation within the PDMS microchannels under confined conditions. The analysis of bacterial morphology and gene expression in response to chemical stimuli, such as isopropyl‐β‐D‐thiogalactopyranoside (IPTG) gradients, demonstrates that the chemical environment has a substantial impact; filamentous cells aligned along the creases. These results illustrate the efficacy of parallel concentric wrinkled PDMS patterns in establishing regulated conditions for investigating microbial behavior and represent significant contributions to the fields of microbiology and biomedicine.

Benchmark dose determining airborne crystalline silica particles based on A549 lung-cell line survival in an in vitro study

Crystalline silica has emerged as a prominent occupational toxicant over extended periods, leading to the development of lung disease and cancer. The objective of this investigation is to establish a benchmark dose (BMD) for crystalline silica micro and nanoparticles based on the dehydrogenase activity of the A549 lung-cell line. The impact of exposure to crystalline silica micro-particles (C–SiO2 MPs) and crystalline silica nanoparticles (C–SiO2 NPs) on A549 epithelial lung cells was examined for durations of 24 and 72 h to evaluate cell viability using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The determination of dose-response and BMD was carried out through the BMD software v 3.2. The findings reveal a dose-dependent relationship between cell viability and both C–SiO2 MPs and -NPs. The BMDL values for 24 h treatment of C–SiO2 MPs and -NPs were determined to be 2.26 and 0.97 µg/ml, respectively, based on exponential models. Correspondingly, these values were found to be 1.17 and 0.85 µg/ml for the 72 h treatment. This investigation underscores the significance of particle size as a contributing factor in assessing occupational health risks. Moreover, the utilization of BMDL can facilitate the determination of more precise values for occupational exposures by considering various parameters associated with particle presence.

3D inkjet printing of hybrid electroactive ink based on molecularly imprinted polymers for lipopolysaccharides detection

A hybrid electroactive ink based on molecularly imprinted polymer (MIP) hollow microparticles, zinc oxide nanoparticles (ZnO NPs) and conductive carbon paste (CP) is reported herein for the first time. The MIP/ZnO NPs/CP and corresponding non-imprinted NIP/ZnONPs/CP modified inks were screen-printed on plastic substrates via 3D inkjet technology to cover around 40 working screen-printed carbon electrodes (SPCE) pieces in a single batch. The custom-made electrochemical MIP/ZnONPs/CP@SPCE sensor was designed for the detection of bacterial endotoxins, i.e., lipopolysaccharides (LPS), derived from Pseudomonas aeruginosa. Hollow MIP silica microparticles with specific properties for 3D printing application, in terms of granulation and morphology, were synthesized via sol-gel method using tetraethyl orthosilicate and (3-aminopropyl) triethoxysilane as monomers. Following the structural and morphological characterization of microparticles, the evaluation of template rebinding indicated a clear specificity of MIPs for LPS compared to the NIPs. Hybrid MIP/ZnONPs/CP and NIP/ZnONPs/CP inks were characterized using morphological and structural methods, which confirmed a viscosity of 25.000 mPa.s, a granulation of <20 µm, and a solid powder content of <27 %, as well as a homogenous incorporation of MIP particles and ZnONPs in the conductive CP. Finally, the electrochemical evaluation of the modified MIP/ZnONPs/CP@SPCE sensor revealed a good sensitivity to LPS molecules in PBS at pH 7.4, in the linear working range 1 - 100 µM, where a 0.058 µM limit of detection (LOD) and a response time less than or equal to 1 min were determined. The selectivity of the MIP/ZnONPs/CP@SPCE sensor towards LPS from Salmonella enterica and Escherichia coli was also assessed, highlighting a clear difference between these structural resembling species.

Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200–2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1–20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.

Facile One Pot Synthesis of Hybrid Core-Shell Silica-Based Sensors for Live Imaging of Dissolved Oxygen and Hypoxia Mapping in 3D Cell Models.

Fluorescence imaging allows for noninvasively visualizing and measuring key physiological parameters like pH and dissolved oxygen. In our work, we created two ratiometric fluorescent microsensors designed for accurately tracking dissolved oxygen levels in 3D cell cultures. We developed a simple and cost-effective method to produce hybrid core-shell silica microparticles that are biocompatible and versatile. These sensors incorporate oxygen-sensitive probes (Ru(dpp) or PtOEP) and reference dyes (RBITC or A647 NHS-Ester). SEM analysis confirmed the efficient loading and distribution of the sensing dye on the outer shell. Fluorimetric and CLSM tests demonstrated the sensors' reversibility and high sensitivity to oxygen, even when integrated into 3D scaffolds. Aging and bleaching experiments validated the stability of our hybrid core-shell silica microsensors for 3D monitoring. The Ru(dpp)-RBITC microparticles showed the most promising performance, especially in a pancreatic cancer model using alginate microgels. By employing computational segmentation, we generated 3D oxygen maps during live cell imaging, revealing oxygen gradients in the extracellular matrix and indicating a significant decrease in oxygen level characteristics of solid tumors. Notably, after 12 h, the oxygen concentration dropped to a hypoxic level of PO2 2.7 ± 0.1%.

(Invited) Electron Transport in Nanocarbon Networks for Energy Conversion and Storage Applications

Carbon nanostructures have attracted great attention in recent years as novel electrode materials in batteries with increased capacity and conductivity as well as enhanced material stability. In these nanostructures, nanocarbons such as carbon nanotubes and graphene nanoplatelets are interconnected to construct their three-dimensional networks around the host materials for Li deposition. This work focuses on the study of electron transport phenomena in these nanocarbon networks with two model material systems: (1) single-walled carbon nanotube (SWCNT) networks co-embedded with silica microparticles (Fig. (a)), and (2) free-standing three-dimensional graphene (3DG) structures with polymeric surface modifications (Fig. (b)). We characterize the materials for electrical conductivity and thermopower with varying material contents in the composites to reveal several key factors determining their energy-dependent carrier transport characteristics. It is found that in these three-dimensional nanocarbon networks, carrier tunneling at the junctions between nanocarbons along with the network morphology predominantly determines the transport properties. Simultaneous increase in electrical conductivity and thermopower is achieved for SWCNT networks co-embedded with silica microparticles by increasing silica content up to 40 w.t.% at a fixed CNT content. The enhanced electron transport is attributed to the reduced junction distances due to the intimate network formation on the surface of silica particles with a polymer binder. Our transport theory based on the Landauer formalism for junction tunneling reveals that the junction modification with polymer can alter the potential barrier heights for both electrons and holes at the junction to significantly change the transport properties of the composite. Doping of nanocarbons is also investigated for their impacts on the junction transport and the geometric factor of the networks. Finally, we also investigate the use of these carbon nanostructures in solid-state thermoelectric (TE) energy harvesters and ionic TE capacitors to harvest thermal energy from temperature gradients and fluctuations. Figure 1

Unraveling the cellular mechanisms of tissue regeneration based on colloidal supraball bio-adhesives

Spherical aggregates of biocompatible mesoporous silica nanoparticles, known as supraballs (SBs), have been proposed as promising tissue adhesives, offering enhanced adhesion energy owing to their high specific surface area. Herein, we investigated the wound-healing mechanism of SBs achieved through nano-bridging at a cellular level. Lap shear tests on porcine skin exhibited improved wet adhesion as SB concentration increased. At 10 wt%, the adhesion strength reached approximately 37 kPa, surpassing that of fibrin glue (∼26 kPa). Hemocompatibility assessments showed non-hemolytic effects for both silica microparticles and SBs. In addition, SBs were validated to be biocompatible, exhibiting low immunogenicity, normal cell proliferation and migration, and degradability in cell media. In vivo results demonstrated that SB-treated wounds displayed accelerated wound closure, accompanied by earlier angiogenesis and low immune response, underscoring the potential of SBs as an effective tissue binder. Further investigation of the healing mechanism was conducted by analyzing differentially expressed genes in cells representing epidermal and dermal areas, revealing notable distinctions between control and SB-treated samples. These variations are associated with cellular behavior and microvascular endothelial cell and keratinocyte proliferation. Taken together, these findings indicate that SBs have the capability to serve as efficient tissue adhesives.

Hyperconfined bio-inspired Polymers in Integrative Flow-Through Systems for Highly Selective Removal of Heavy Metal Ions

Access to clean water, hygiene, and sanitation is becoming an increasingly pressing global demand, particularly owing to rapid population growth and urbanization. Phytoremediation utilizes a highly conserved phytochelatin in plants, which captures hazardous heavy metal ions from aquatic environments and sequesters them in vacuoles. Herein, we report the design of phytochelatin-inspired copolymers containing carboxylate and thiolate moieties. Titration calorimetry results indicate that the coexistence of both moieties is essential for the excellent Cd2+ ion-capturing capacity of the copolymers. The obtained dissociation constant, KD ~ 1 nM for Cd2+ ion, is four-to-five orders of magnitude higher than that for peptides mimicking the sequence of endogenous phytochelatin. Furthermore, infrared and nuclear magnetic resonance spectroscopy results unravel the mechanism underlying complex formation at the molecular level. The grafting of 0.1 g bio-inspired copolymers onto silica microparticles and cellulose membranes helps concentrate the copolymer-coated microparticles in ≈3 mL volume to remove Cd2+ ions from 0.3 L of water within 1 h to the drinking water level (<0.03 µM). The obtained results suggest that hyperconfinement of bio-inspired polymers in flow-through systems can be applied for the highly selective removal of harmful contaminants from the environmental water.

Separation and purification of hyaluronic acid by [formula omitted] nano and micro particles coated with chitosan and silica

Hyaluronic acid (HA), a glycosaminoglycan, is comprised of alternating units of D-glucuronic acid and N-acetylglucosamine. This compound harbors numerous biomedical applications, including its use in pharmaceuticals, wound healing, osteoarthritis treatment, and drug delivery. Its unique composition and exceptional features, such as its high water-absorbing and retaining capacity, have also led to its use in the cosmetics industry. The employment of this biopolymer has given rise to an escalation in the request for its manufacture. The present investigation has explored the correlation between hyaluronic acid and chitosan and silica for the purpose of separation. Consequently, Iron oxide magnetic nano particles and micro particles were produced via co-precipitation method and were layered with chitosan and silica to purify the hyaluronic acid from the fermentation broth that was generated by Streptococcus Zooepidemicus. The size distribution and zeta potentials of the two kinds of particles were gauged with the aid of a dynamic laser light scattering apparatus and zeta potential meter (Malvern, Zeta master) respectively. The confirmation of the chemical structure of the Fe3O4 nanoparticles and Fe3O4 particles conjugated with chitosan and silica was accomplished through the utilization of Fourier Transform Infrared Spectroscopy (FT-IR). Protein contamination was thoroughly characterized by means of sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Nanodrop 2000/2000c spectrophotometers protein estimation method. The maximum HA adsorption capacity, under optimal pH conditions of 4, was determined to be 87 mg/g, 112 mg/g, 51 mg/g, and 44 mg/g for Fe3O4 −chitosan nanoparticle, Fe3O4 −chitosan micro particle, Fe3O4 −silica microparticle, and Fe3O4 −silica nanoparticle, respectively.

Different rheological behaviors of reinforced poly(methylvinylsiloxane) by mesoporous and spherical silica microparticles

To elucidate the mechanism underlying the high performance of mesoporous silica aerogel microparticle (SAG) in reinforcing polymers, the hydrodynamic effect and reinforcement effect of SAG microparticle in Poly-methylvinylsiloxane (PMVS) were investigated. For comparison, regular spherical silica particles (SS) with a comparable particle size and smooth surface were also incorporated into the study as a contrasting filler. It was found that SAG tended to form aggregates with high aspect ratio (shape factor f values between 16-20) and highly branched backbone structures (x = 1.95). However, these aggregates are more loosely packed (df = 1.7) and easily break into smaller flocs under the influence of shear forces. The load-bearing mechanism of the spatial network formed by these aggregates as nodes was akin to physical gels controlled by bond-bending forces (BBFs), with a scaling exponent of G*r with φe-φc of ν = 3.84, close to the theoretical value of the BBFs model. In contrast, the SS particles formed more compact aggregates (f value approximately 1.6) in PMVS, with load-bearing characteristics of the spatial network formed by them closer to chemical gels controlled by central forces (CFs). The scaling exponent of G*r with φe-φc for SS/PMVS was found to be ν = 2.15, close to the theoretical value of the CFs model.

Development of an efficient, effective, and economical technology for proteome analysis

We present an efficient, effective, and economical approach, named E3technology, for proteomics sample preparation. By immobilizing silica microparticles into the polytetrafluoroethylene matrix, we develop a robust membrane medium, which could serve as a reliable platform to generate proteomics-friendly samples in a rapid and low-cost fashion. We benchmark its performance using different formats and demonstrate them with a variety of sample types of varied complexity, quantity, and volume. Our data suggest that E3technology provides proteome-wide identification and quantitation performance equivalent or superior to many existing methods. We further propose an enhanced single-vessel approach, named E4technology, which performs on-filter in-cell digestion with minimal sample loss and high sensitivity, enabling low-input and low-cell proteomics. Lastly, we utilized the above technologies to investigate RNA-binding proteins and profile the intact bacterial cell proteome.

Assessment of acoustic shock wave resistance of SiO2 (α-cristobalite): A potential material for aerospace and defense industry applications

In the present research article, the acoustic shock wave-resistant efficiency of silica microparticles (SiO2-α-cristobalite)) has been experimentally evaluated in terms of structural, optical and morphological stability against the impact of shock waves. The required SiO2 particles were synthesized by a hydrothermal method which was subjected to a different number of shock pulses such as 200,400 and 600 with Mach number 2.2. Shocked samples’ structural, morphological and optical stabilities have been evaluated by utilizing a powder X-ray diffractometer (PXRD), Ultraviolet–Diffuse reflectance spectrometer (DRS) while the surface morphological analysis has been scrutinized by the field emission scanning electron microscopic technique (FESEM) and transmission electron microscopy (TEM). X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy techniques are utilized to evaluate oxidation states and crystallographic structural stability. The above-mentioned analytical techniques provide convincing proofs whereby the synthesized SiO2 particles are authentically proven to possess outstanding structural, optical and morphological stability against the impact of shock waves. The implicated experimental results and the arguments strongly suggest that the SiO2 particles are suitable candidates for aerospace and defense industry applications due to their outstanding shock wave-resistant properties.

Major food constituents influence the antibacterial activity of vanillin immobilized onto silicon microparticles against Escherichia coli

Antimicrobial filtration materials based on essential oil components (EOCs) immobilized onto silicon oxide particles have been found effective for nonthermal stabilization of liquid foods (i.e., beer, juice, wine, and etc.). However, their antimicrobial efficiency depends on the food matrix. The present work aimed to assess the effect of the major constituents of liquid food matrices on the antimicrobial activity of vanillin immobilized onto silica microparticles. Silicon oxide particles were functionalized with vanillin and characterized. The maximum tolerated concentrations of different food major constituents (i.e., proteins, lipids, carbohydrates, organic acids, alcohols and minerals) were determined against Escherichia coli K12. The results showed that organic acid and alcohol had synergetic effects on vanillin-functionalized particles, and the addition of proteins, lipids or some carbohydrates inhibited their antimicrobial activity. No effects on microbial counts were found for mineral salts. The dual combinations between the synergistic and nonsynergistic food constituents showed improved antimicrobial activity compared to single compounds. The data confirmed previous in vitro experiments and could be used to predict the antimicrobial activity of the filtration system when treating real liquid food matrices.

Enhanced Oxygen Mass Transfer in Mixing Bioreactor Using Silica Microparticles

This work aimed to improve the oxygen transfer mass coefficient (kLa) in mixing reactors, first evaluating the effect of agitation and aeration and then evaluating the influence of the size and concentration of silica microparticles. Silicon dioxide synthesized via the sol-gel technique, commercial sand, and beach sand were characterized by particle size distribution, scanning electron microscopy, XRD, EDS, FTIR, TG/DTA, and BET. The particles presented average values of approximately 9.2, 76.9, 165.1, and 364.4 µm, with irregular surfaces and different roughness. Silica sol-gel is amorphous while beach and commercial sand have a crystalline structure consisting of silicon, oxygen, and carbon residues. Silica sol-gel presents a higher loss of mass and surface area than other silica microparticles, with a shallow mass loss and a smaller surface. Increasing aeration and agitation improves the kLa, as well as adding silica microparticles. The best kLa was found using silica microparticles with approximately 75 µm concentrations of 1.0 g L−1 (silica sol-gel) and 2.0 g L−1 (commercial and treated beach sand). All silica microparticles used in this work improve mass transfer performance in mixing bioreactors.

Size Tuning of Mesoporous Silica Adjuvant for One-Shot Vaccination with Long-Term Anti-Tumor Effect.

Despite recent clinical successes in cancer immunotherapy, it remains difficult to initiate a long-term anti-tumor effect. Therefore, repeated administrations of immune-activating agents are generally required in most cases. Herein, we propose an adjuvant particle size tuning strategy to initiate a long-term anti-tumor effect by one-shot vaccination. This strategy is based on the size-dependent immunostimulation mechanism of mesoporous silica particles. Hollow mesoporous silica (HMS) nanoparticles enhance the antigen uptake with dendritic cells around the immunization site in vivo. In contrast, hierarchically porous silica (HPS) microparticles prolong cancer antigen retention and release in vivo. The size tuning of the mesoporous silica adjuvant prepared by combining both nanoparticles and microparticles demonstrates the immunological properties of both components and has a long-term anti-tumor effect after one-shot vaccination. One-shot vaccination with HMS-HPS-ovalbumin (OVA)-Poly IC (PIC, a TLR3 agonist) increases CD4+ T cell, CD8+ T cell, and CD86+ cell populations in draining lymph nodes even 4 months after vaccination, as well as effector memory CD8+ T cell and tumor-specific tetramer+CD8+ T cell populations in splenocytes. The increases in the numbers of effector memory CD8+ T cells and tumor-specific tetramer+CD8+ T cells indicate that the one-shot vaccination with HMS-HPS-OVA-PIC achieved the longest survival time after a challenge with E.G7-OVA cells among all groups. The size tuning of the mesoporous silica adjuvant shows promise for one-shot vaccination that mimics multiple clinical vaccinations in future cancer immunoadjuvant development. This study may have important implications in the long-term vaccine design of one-shot vaccinations.

Versatile and Remotely Controllable Light-Induced Coagulation of Particles Under Flow in a 2D Channel.

On-demand switch on/off blood clogging is of paramount importance for the survival of mammals, for example as a quick response to seal damage wounds to minimize their bleeding rate. This mechanism is a complex chain process from initiated red blood cell aggregation at the target location (open wound) that quickly seals on a macroscopic scale the damaged flash. Inspired by nature an on-demand switchable particle clogging mechanism is developed with high spatial resolution down to micrometer size using light as an external non-invasive stimulation. Particle clogging can be adjusted on demand strong enough to even withstand pressure-driven fluid flow, additionally building up walls of aggregated particles, which stop the momentum of big particles under shear. The principle relies on a photosensitive surfactant, which induces under light illumination a long-ranged lateral attractive phoretic-osmotic activity of silica microparticles forcing them to aggregate. The strength of aggregation and therefore motion reduction or even stop of the particles against the fluid flow depends on the ratio between the aggregation strength and the velocity of the particles. The aggregation strength can be precisely controlled by the applied light intensity and adjusted particle concentration. Increasing both parameters results in a stronger aggregation tendency.