Agarose Hydrogel Research Articles

UiO-66-NH2 initiated cascade reaction: Constructing a ratiometric fluorescence sensor for ultrasensitive detection of nerve agent simulant

BackgroundHighly toxic organophosphorus nerve agents often exist in the form of gas in the environment and can damage human neuroregulatory system by inhibiting the activity of acetylcholinesterase (AChE). However, fluorescent probes based on small organic molecules bring a secondary burden to environment, and their sensitivity and specificity for sarin simulant diethyl chlorophosphate (DCP) detection are unsatisfactory. Nanozyme cascade systems with signal amplification can be used for highly sensitive identification of analytes, but are rarely used in ratiometric analysis of DCP. Combination of enzyme cascades and ratiometric fluorescence ensures the accuracy and sensitivity of the output signal. ResultsWe prepared a self-assembled nanohybrid (Ag–AuNCs@UiO-66-NH2) by metal-organic framework material and gold nanoclusters. On the one hand, UiO-66-NH2 with enzyme-like activity was used to hydrolyze DCP into diethyl phosphate (DEP) and chloridion (Cl−). Cl− hindered aggregation-induced enhanced emission (AIEE) of AuNCs by binding with Ag+ and decreased the fluorescence of AuNCs. On the other hand, ligand metal charge transfer effect (LMCT) of UiO-66-NH2 was blocked by DCP to enhance the fluorescence of UiO-66-NH2. Combining ratiometric analysis and nanozyme cascade reaction, an ultra-sensitive fluorescence sensor for detecting DCP was constructed, and ensured the accuracy of experimental results. In addition, Ag–AuNCs@UiO-66-NH2 was embedded into the agarose hydrogel substrate, the resulting agarose hydrogel film allowed quantitative assessment of DCP vapor and high sensitivity was demonstrated (detection limit as low as 1.02 ppb). SignificanceA strategy combining enzyme cascade with ratiometric fluorescence was proposed, which improved the accuracy and sensitivity of the analysis results. The soft-solid platform based on agarose hydrogel film was constructed to realize the quantitative monitoring of sarin simulant gas. The LOD value obtained in this work is much lower than the immediately life-threatening or health threatening concentration of sarin.

Atomic Force Microscopy (AFM) Tip based Nanoelectrode with Hydrogel Electrolyte and Application to Single-Nanoparticle Electrochemistry

<p>An unconventional fabrication technique of nanoelectrode was developed using atomic force microscopy (AFM) and hydrogel. Until now, the precise control of electroactive area down to a few nm<sup>2</sup> has always been an obstacle, which limits the wide application of nanoelectrodes. Here, the nanometer-sized contact between the boron-doped diamond (BDD) as conductive AFM tip and the agarose hydrogel as solid electrolyte was well governed by the feedback amplitude of oscillation in the non-contact mode of AFM. Consequently, this low-cost and feasible approach gives rise to new possibilities for the fabrication of nanoelectrodes. The electroactive area controlled by the set point of AFM was investigated by cyclic voltammetry (CV) of the ferrocenmethanol (FcMeOH) combined with quasi-solid agarose hydrogel as an electrolyte. Single copper (Cu) nanoparticle was deposited at the apex of the AFM tip using this platform whose electrocatalytic activity for nitrate reduction was then investigated by CV and Field Emission-Scanning Electron Microscopy (FE-SEM), respectively.</p>

Nonspecific membrane-matrix interactions influence diffusivity of lipid vesicles in hydrogels

The diffusion of extracellular vesicles and liposomes in vivo is affected by different tissue environmental conditions and is of great interest in the development of liposome-based therapeutics and drug-delivery systems. Here, we use a bottom-up biomimetic approach to better isolate and study steric and electrostatic interactions and their influence on the diffusivity of synthetic large unilamellar vesicles in hydrogel environments. Single-particle tracking of these extracellular vesicle-like particles in agarose hydrogels as an extracellular matrix model shows that membrane deformability and surface charge affect the hydrogel pore spaces that vesicles have access to, which determines overall diffusivity. Moreover, we show that passivation of vesicles with PEGylated lipids, as often used in drug-delivery systems, enhances diffusivity, but that this effect cannot be fully explained with electrostatic interactions alone. Finally, we compare our experimental findings with existing computational and theoretical work in the field to help explain the nonspecific interactions between diffusing particles and gel matrix environments.

Ionic Strength Impacts the Physical Properties of Agarose Hydrogels.

Agarose is a natural polysaccharide known for its ability to form thermoreversible hydrogels. While the effects of curing temperature and polysaccharide concentration on mechanical properties have been discussed in the literature, the role of ionic strength has been less studied. In the present manuscript, we investigate the effects of supporting salt concentration and the role of cation (i.e. Na+ or Li+, neighbors in the Hofmeister series), on the setting and performance of agarose hydrogels. Compressive and rheological measurements show that the supporting salts reduce the immediate elastic response of agarose hydrogels, with Li+ showing a stronger effect than Na+ at high ionic strength, while they significantly increase the extent of linear stress-strain response (i.e., linear elasticity). The presence of increasing amounts of added supporting salt also leads to a reduction in hysteresis during mechanical deformation due to loading and unloading cycles, which is more pronounced with Li+ than with Na+. The combination of rheological measurements and NMR relaxometry shows a mesh size in agarose hydrogels in the order of 6-17 nm, with a thickness of the water layer bound to the biopolymer of about 3 nm. Of note, the different structuring of the water within the hydrogel network due to the different alkali seems to play a role for the final performance of the hydrogels.

Coordinated carbon dots-Fe featuring synergistically enhanced peroxidase-like activity at neutral pH for specific and background-free detection of dichlorvos

Nanozyme-based assays present favorable prospects in sensitive determination of pesticides in food samples yet are constrained with little or even no catalytic activities at neutral pH, lack of selectivity, and interference by sample color. Here, a facile and novel photothermal system for rapid, specific, sensitive, and background-free detection of dichlorvos was developed based on peroxidase-like activity of coordinated carbon dots-Fe (CDs-Fe). CDs-Fe was prepared and fabricated based on the redox and coordination chemistry between CDs and Fe species. Catalytic mechanism investigations illustrate that CDs-Fe with outstanding peroxidase-like activity at neutral pH comes from the synergistic effect of •OH production and electron transfer process. More interestingly, dichlorvos can specifically complex with CDs-Fe through electrostatic attraction and π-π stacking interactions, which then cement substrates affinity and improve electron transfer efficiency to enhance the catalytic activity. Oxidized 3,3′,5,5′-tetramethylbenzidine (oxTMB) presents photothermal effect by absorption of near-infrared (808 nm) laser-driven light, which eliminates the color interference from real samples. Accordingly, a background-free photothermal strategy was established. Furthermore, a portable hydrogel kit was fabricated by embedding CDs-Fe and TMB into agarose hydrogel for on-site rapid detection of dichlorvos. A good relationship was observed in the range of 5.00–650 μg L−1 with a satisfactory detection limit at 4.85 μg L−1, and a good recovery (90.56–107.0 %) with excellent anti-interference capacity was achieved for real sample analysis. The work presents a novel nanozyme enhancement strategy for specific and background-free detecting dichlorvos in food samples.

Application of photocrosslinked gelatin, alginate and dextran hydrogels in the in vitro culture of testicular tissue

Testicular tissue culture in vitro is considered an important tool for the study of spermatogenesis and the treatment of male infertility. Although agarose hydrogel is commonly used in testicular tissue culture, the efficiency of spermatogenesis in vitro is limited. In this study, testicular tissues from adult mice were cultured using a gas-liquid interphase method based on agarose (Agarose), gelatin methacryloyl (GelMA), alginate methacryloyl (AlgMA), dextran methacryloyl (DexMA), and mixture GelMA-Agarose, AlgMA-Agarose, and DexMA-Agarose hydrogels, respectively, for 32 days in vitro. The integrity of the seminiferous tubules, the density and proportions of spermatogonia, spermatocytes, Sertoli cells, and testosterone concentrations were quantified and compared between groups. Properties of different hydrogels including compression modulus, Fourier Infrared Spectroscopy (FITR) spectra, pore size, water absorption, and water retention were tested to investigate how biochemical and physical properties of hydrogels affect the results of testicular tissue culture. The results indicate that testicular tissues cultured on AlgMA exhibited the highest seminiferous tubule integrity rate (0.835 ± 0.021), the presence of a high density of spermatocytes (2107.627 ± 232.082/mm2), and a high proportion of SOX9-positive well-preserved seminiferous tubules (0.473 ± 0.047) compared to all remaining experimental groups on day 32. This may be due to the high water content of AlgMA reducing the toxic effect of oxygen on testicular tissue. In the later period of culture, testicular tissues cultured on DexMA, not DexMA-Agarose, produced significantly more testosterone (18.093 ± 3.302 ng/mL) than the other groups, suggesting that DexMA is friendly to Leydig cells. Our study provides a new idea for the optimization of the gas-liquid interphase method for achieving in vitro spermatogenesis, facilitating the future achievement of efficient in vitro spermatogenesis in more species, including humans.

Macro-indentation testing of soft biological materials and assessment of hyper-elastic material models from inverse finite element analysis

Mechanical characterization of hydrogels and ultra-soft tissues is a challenging task both from an experimental and material parameter estimation perspective because they are much softer than many biological materials, ceramics, or polymers. The elastic modulus of such materials is within the 1 - 100 kPa range, behaving as a hyperelastic solid with strain hardening capability at large strains. In the current study, indentation experiments have been performed on agarose hydrogels, bovine liver, and bovine lymph node specimens. This work reports on the reliable determination of the elastic modulus by indentation experiments carried out at the macro-scale (mm) using a spherical indenter. However, parameter identification of the hyperelastic material properties usually requires an inverse finite element analysis due to the lack of an analytical contact model of the indentation test. Hence a comprehensive study on the spherical indentation of hyperelastic soft materials is carried out through robust computational analysis. Neo-Hookean and first-order Ogden hyperelastic material models were found to be most suitable. A case study on known anisotropic hyperelastic material showed the inability of the inverse finite element method to uniquely identify the whole material parameter set.

A Transparent Hydrogel-Ionic Conductor with High Water Retention and Self-Healing Ability.

This study presents a transparent and ion-conductive hydrogel with suppressed water loss. The hydrogel comprises agarose polymer doped with sucrose and sodium chloride salt (NaCl-Suc/A hydrogel). Sucrose increases the water retention of the agarose gel, and the Na and Cl ions dissolved in the gel provide ionic conductivity. The NaCl-Suc/A gel shows high retention capability and maintains a 45% water uptake after 4 h of drying at 60 °C without encapsulation at the optimum gel composition. The doped NaCl-Suc/A hydrogel demonstrates improved mechanical properties and ionic conductivity of 1.6 × 10-2 (S/cm) compared to the pristine agarose hydrogel. The self-healing property of the gel restores the electrical continuity when reassembled after cutting. Finally, to demonstrate a potential application of the ion-conductive hydrogel, a transparent and flexible pressure sensor is fabricated using the NaCl-Suc/A hydrogel, and its performance is demonstrated. The results of this study could contribute to solving problems with hydrogel-based devices such as rapid dehydration and poor mechanical properties.

A recyclable hydrogel-based sustained release system for formaldehyde monitoring in foods.

In this work, 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (AHMT) was pre-doped into agarose hydrogels; consequently, sustained hydrogel systems with modulated release performance were constructed for simple operation and recyclability in point-of-care detection of formaldehyde (FA). With the increase in FA concentrations, the absorbance response of the supernatant solutions showed linear relationships and the color of the reaction mixtures gradually increased. The detection limit was calculated to be 0.013 μg mL-1. To verify its practical application, a simple, rapid and low-cost FA detection platform was built on the basis of the optimized conditions, and the method shows the merits of simplicity, high sensitivity and selectivity. More importantly, the developed hydrogels are recyclable and can be used at least five times without any loss in sensing performance. Significantly, the sensory hydrogels can be employed by non-skilled people for monitoring food safety and applied for the practical detection of FA in foods.

Expression of concern: Investigation of the biological activity, mechanical properties and wound healing application of a novel scaffold based on lignin–agarose hydrogel and silk fibroin embedded zinc chromite nanoparticles

Expression of concern for ‘Investigation of the biological activity, mechanical properties and wound healing application of a novel scaffold based on lignin–agarose hydrogel and silk fibroin embedded zinc chromite nanoparticles’ by Reza Eivazzadeh-Keihan et al., RSC Adv., 2021, 11, 17914–17923, https://doi.org/10.1039/D1RA01300A.

Diffusion and Interaction Studies of Dye in Agarose Hydrogel Enriched with TiO₂ Nanoparticles: A Temperature-Dependent Analysis

Abstract: The objective of this work is to examine the interactions and diffusion properties of a conventional dye inside an agarose hydrogel that has been enhanced with titanium dioxide (TiO2) nanoparticles. The experiment is carried out at three specific temperatures (30°C, 40°C, and 50°C) and three varying values of concentration (0.2, 0.5, and 1 mg/g). Utilizing Fick’s equations of diffusion, we successfully calculated the surface concentrations (Cs) and effective diffusion coefficients (D) based on the experimental results. The influence of TiO2 nanoparticles on dye diffusion rates was shown by the observed drop in diffusion coefficients with proportional rise in the number of nanoparticles. Both the diffusion coefficient and the surface concentration have a propensity to enhance with an elevation in temperature. The results indicate that the distribution of pigments in hydrogels improved with TiO2 is controlled by temperature variability. The aforementioned discovery implies that the results might be used in controlled release systems, wastewater treatment, and materials research.

Visualized sensing of erythritol using a simple enzyme-free catechol-based hydrogel film.

Based on the versatile properties of bio-derived materials, non-enzymatic assays in combination with electronic devices have attracted increasing interest. Here, we report a novel enzyme-free visualization approach for the detection of erythritol, which is a zero-calorie natural sweetener and serves as an ideal sucrose substitute for diabetics or overweight people who need sugar control. The recognition element of the electrochemical biosensor was constructed by catechol modification on a chitosan-based hydrogel film. The signal transduction was achieved by the competitive binding assay of sweeteners. The results show that 2-fluorophenylboronic acid (FPBA) can form a cyclic boronate ester with the ortho-hydroxyls of both reduced catechol and oxidized quinone, impeding the electron transfer and leading to redox signal attenuation. The addition of sweeteners caused a competitive reaction resulting in bonding between the 1,2-diols and FPBA moieties, and in the recovery of the redox signals. Importantly, the pattern of redox signal changes of catechol can be detected optically, as the oxidized quinone state is darker in color than the reduced catechol state. Using a simple cell phone imaging application, we demonstrate that erythritol can be distinguished from other sweeteners in real samples using the oxidized catechol-Chit0/agarose hydrogel film. Thus, we envision that this method could allow diabetics and people who need to control their sugar intake to detect whether the product contains only erythritol in the field or at home. In addition, this work further illustrates the potential of bio-derived materials for performing redox-based functions and enzyme-free visualization assays.

Priming chondrocytes during expansion alters cell behavior and improves matrix production in 3D culture

ObjectiveCartilage tissue engineering strategies that use autologous chondrocytes require in vitro expansion of cells to obtain enough cells to produce functional engineered tissue. However, chondrocytes dedifferentiate during expansion culture, limiting their ability to produce chondrogenic tissue and their utility for cell-based cartilage repair strategies. The current study identified conditions that favor cartilage production and the mechanobiological mechanisms responsible for these benefits. DesignChondrocytes were isolated from juvenile bovine knee joints and cultured with (primed) or without (unprimed) a growth factor cocktail. Gene expression, cell morphology, cell adhesion, cytoskeletal protein distribution, and cell mechanics were assessed. Following passage 5, cells were embedded into agarose hydrogels to evaluate functional properties of engineered cartilage. ResultsPriming cells during expansion culture altered cell phenotype and chondrogenic tissue production. Unbiased RNA-sequencing analysis suggested, and experimental studies confirmed, that growth factor priming delays dedifferentiation associated changes in cell adhesion and cytoskeletal organization. Priming also overrode mechanobiological pathways to prevent chondrocytes from remodeling their cytoskeleton to accommodate the stiff, monolayer microenvironment. Passage 1 primed cells deformed less and had lower YAP1 activity than unprimed cells. Differences in cell adhesion, morphology, and cell mechanics between primed and unprimed cells were mitigated by passage 5. ConclusionsPriming suppresses mechanobiologic cytoskeletal remodeling to prevent chondrocyte dedifferentiation, resulting in more cartilage-like tissue-engineered constructs

Towards sustainable antimicrobials from plants: Some ways to abridge current methodological approaches

Plants are potential sources for new antimicrobials that might be helpful in combating antimicrobial resistance. Screening of plant materials for antimicrobial activities is an essential step towards discovery of new alternatives to current antibiotics. This article presents strategies allowing to simplify some methodological approaches used in initial testing of plant materials for their antimicrobial properties. Particular attention is given to sensitivity testing without extraction based on utilisation of agarose hydrogel tablets and dry powders. Other aspects relate to testing fractionated extracts and rapid determination of inhibition modes directly from zones of inhibition in diffusion assays. Using these approaches could facilitate standardised preliminary screening for new antimicrobials to make this process more productive.

An ultrafast and highly sensitive fluorescent probe for the detection of HSO3− and its application in food samples and SO2 gas

SO2 is one of the main components of air pollution gas, its derivatives HSO3− and SO32− were considerable used as food additive because of their antiseptic and bacteriostatic effects. Excessive intake of HSO3− is harmful to human health, so it is extremely important to detect the content of HSO3− in food sample by effective method. In this work, a small molecular fluorescence probe TPE-O based on tetraphenylethene fluorophore was designed and synthesized. The probe showed ultrafast (< 3 s) and obvious colorimetric response to HSO3− with high selectivity and sensitivity (LOD = 210 nM). The possible Michael-type addition of HSO3− on the activated C = C bond blocked the π-conjugated system, thus lead to changes in fluorescence and absorption spectra. Probe TPE-O not only can detect the content of HSO3− in sugar and wine, but also can be loaded on agarose hydrogel to detect SO2 gas. Therefore, this work provided a powerful tool for the detection of HSO3− in food samples and SO2 gas.

Factors affecting diffusion of polar organic compounds in agarose hydrogel applied to control mass transfer in passive samplers.

Diffusive hydrogel-based passive sampler (HPS) based on diffusive gradients in thin films (DGT) is designed for monitoring polar organic contaminants in the aquatic environment. DGT technique controls the compound's overall uptake rate by adding a hydrogel layer of known thickness, which minimizes the importance of the resistive water boundary layer in the compound uptake process. In this work, we investigated several factors which may influence the diffusion of a range of aquatic contaminants in 1.5% agarose hydrogel. Diffusion in hydrogel was tested using the sheet stacking method. We demonstrated that a thin nylon netting incorporated into the diffusive hydrogel for mechanical strengthening does not significantly affect the diffusion of 11 perfluoroalkyl compounds. Further, we investigated the effect of pH in the range from 3 to 11 on the diffusion of a range of 39 aromatic amines (AAs)-36 aromatic, 2 aliphatic, and azobenzene in hydrogel. AAs were chosen as representatives of compounds with pH-dependent dissociation in water. Analysis of variance showed no significant difference in meandiffusion coefficient log D value at five pH values. The demonstration that the diffusion coefficient D and thus the sampling rate Rs are independent on pH simplifies the interpretation of data from field studies because we can neglect the influence of pH on the Rs. log D values (m2 s-1) of tested AAs ranged from to - 9.77 for 3,3'-dimethylbenzidine to - 9.19 for azobenzene. A negative correlation of log D with molar mass (log M) and molecular volume (log Vm) was observed (R = - 0.57 and - 0.56, respectively). The diffusion coefficient presents a critical parameter for the sampling rate estimation of HPS. Theoretical sampling rates Rs of AAs were calculated for a HPS using the average D values. TheoreticalRs values calculated for AAs at 22°C ranged from 29 mL day-1 for 3,3'-dimethylbenzidine to 106 mL day-1 for 2-aminopyridine. Our calculated values of Rs are in the same range as those already published for a range of low-molecular polar organic contaminants, which supports the possibility of deriving sampler performance parameters in the field from laboratory-derived diffusivity of analytes in hydrogel.

Solution-free and simplified H&E staining using a hydrogel-based stamping technology.

Hematoxylin and eosin (H&E) staining has been widely used as a fundamental and essential tool for diagnosing diseases and understanding biological phenomena by observing cellular arrangements and tissue morphological changes. However, conventional staining methods commonly involve solution-based, complex, multistep processes that are susceptible to user-handling errors. Moreover, inconsistent staining results owing to staining artifacts pose real challenges for accurate diagnosis. This study introduces a solution-free H&E staining method based on agarose hydrogel patches that is expected to represent a valuable tool to overcome the limitations of the solution-based approach. Using two agarose gel-based hydrogel patches containing hematoxylin and eosin dyes, H&E staining can be performed through serial stamping processes, minimizing color variation from handling errors. This method allows easy adjustments of the staining color by controlling the stamping time, effectively addressing variations in staining results caused by various artifacts, such as tissue processing and thickness. Moreover, the solution-free approach eliminates the need for water, making it applicable even in environmentally limited middle- and low-income countries, while still achieving a staining quality equivalent to that of the conventional method. In summary, this hydrogel-based H&E staining method can be used by researchers and medical professionals in resource-limited settings as a powerful tool to diagnose and understand biological phenomena.

Influence of hydrogel and porous scaffold on the magnetic thermal property and anticancer effect of Fe3O4 nanoparticles

Magnetic hyperthermia uses magnetic nanoparticles (MNPs) for conversion of magnetic energy into thermal energy under an alternating magnetic field (AMF) to increase local temperature for ablation of cancer cells. The magnetic thermal capacity of MNPs not only depends on the intrinsic properties of MNPs but is also affected by the microenvironmental matrices surrounding the MNPs. In this study, the influence of agarose hydrogels and gelatin porous scaffolds on the magnetic thermal property and anticancer effect of Fe3O4 nanoparticles (NPs) were investigated with a comparison to free Fe3O4 NPs. Flower-like Fe3O4 NPs were synthesized and embedded in agarose hydrogels and gelatin porous scaffolds. Under AMF irradiation, the free Fe3O4 NPs had the best magnetic thermal properties and the most efficiently increased the local temperature to ablate breast cancer cells. However, the Fe3O4 NPs embedded in agarose hydrogels and gelatin porous scaffolds showed reduced magnetic-thermal conversion capacity, and the local temperature change was decreased in comparison to free Fe3O4 NPs during AMF irradiation. The gelatin porous scaffolds showed a higher inhibitory influence than the agarose hydrogels. The inhibitory effect of agarose hydrogels and gelatin porous scaffolds on magnetic-thermal conversion capacity resulted in a decreased anticancer ablation capacity to breast cancer cells during AMF irradiation. The Fe3O4 NP-embedded gelatin scaffolds showed the lowest anticancer effect. The results suggested that the matrices used to deliver MNPs could affect their performance, and appropriate matrices should be designed to maximize their therapeutic effect for biomedical applications.

Leveraging Microgels Prepared from Poly(ethylene glycol) Bisepoxide and Polyetheramine for Versatile Surface Structuring of Agarose Hydrogels.

We demonstrate a macromer-type bisepoxide, poly(ethylene glycol) diglycidyl ether, polymerizing readily with a trifunctional polyetheramine Jeffamine T-403 in water to facilitate the development of a series of microgels abbreviated as PMG. Simply by varying the concentration of the as-prepared thermoresponsive intermediate prepolymer from 1 to 2 and 4%, hydrodynamic sizes of the resulting P1MG, P2MG, and P4MG are easily tuned in the submicrometer to micrometer range shown by the dynamic light scattering results. Besides size difference, these microgels also deform differently, where the drying-induced deformation effect is most severe for P1MG and least prominent for P4MG. Simple evaporative deposition of PMG into multilayer packing provides versatile and green options for microgel-mediated surface structuring of agarose hydrogels. Specifically, deformabile P1MG- and P2MG-derived coatings render agarose gel microwrinkle textures by buckling against swelling-induced surface instability. Conversely, stiffer P4MG microgels lead to a patchy patterned hierarchical coating on agarose, similar to the cracking effect in drying colloidal films. The straightforward microgel-on-macrogel strategy allows integration of both wrinkle and patchy patterns to generate Janus-type agarose gels, just by rationally arranging the coating sequence. Diversifying topographic features attainable through microgel-based coatings on hydrogels could potentially make the sustainable and biocompatible material of agarose a more compelling choice for bioapplications. Brief demonstrations of the broad applicability of P1MG toward wrinkling of proteinaceous and synthetic hydrogels further highlight promising prospects of the PMG microgel-on-macrogel functionalization strategy.

Nanoparticle Dynamics in Composite Hydrogels Exposed to Low-Frequency Focused Ultrasound.

Pulsed focused ultrasound (FUS) in combination with microbubbles has been shown to improve delivery and penetration of nanoparticles in tumors. To understand the mechanisms behind this treatment, it is important to evaluate the contribution of FUS without microbubbles on increased nanoparticle penetration and transport in the tumor extracellular matrix (ECM). A composite agarose hydrogel was made to model the porous structure, the acoustic attenuation and the hydraulic conductivity of the tumor ECM. Single-particle tracking was used as a novel method to monitor nanoparticle dynamics in the hydrogel during FUS exposure. FUS exposure at 1 MHz and 1 MPa was performed to detect any increase in nanoparticle diffusion or particle streaming at acoustic parameters relevant for FUS in combination with microbubbles. Results were compared to a model of acoustic streaming. The nanoparticles displayed anomalous diffusion in the hydrogel, and FUS with a duty cycle of 20% increased the nanoparticle diffusion coefficient by 23%. No increase in diffusion was found for lower duty cycles. FUS displaced the hydrogel itself at duty cycles above 10%; however, acoustic streaming was found to be negligible. In conclusion, pulsed FUS alone cannot explain the enhanced penetration of nanoparticles seen when using FUS and microbubbles for nanoparticle delivery, but it could be used as a tool to enhance diffusion of particles in the tumor ECM.