Diffusion Coefficient Of Nanoparticles Research Articles

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.

Micro-scale simulation of adsorption-diffusion behaviors of nanoparticles onto mobile oil/water interface

A novel, hybrid pore-scale simulation method using Lattice-Boltzmann (LB) coupled with Langevin-Dynamics (LD) is proposed to investigate the physics of nanoparticles onto oil/water interface. Based on the LB method, the high-resolution characterization of oil-water interface is established. Then, in a fashion of discrete LB forcing source distribution, the LD method is introduced to characterize the effects of Brownian motion, thermal fluctuation-dissipation, multi-body hydrodynamics, and particle-particle interactions. By the means of the new LB-LD coupling model, the adsorption and diffusion characterization of nanoparticles onto oil/water interface are investigated. Moreover, by introducing the interference coefficient and non-equilibrium time, a modified Langmuir adsorption equation is first established by more accurately quantifying the adsorption characterization of nanoparticles and the consequent impacts onto the oil/water interfacial force (IFT), which cannot be accurately described by the classical Langmuir model. For the example of SiO2 nanoparticles adsorption, it is observed that small-size nanofluids with high concentration could accelerate the adsorption of nanoparticles. In addition, both the lateral and longitudinal diffusion coefficients of nanoparticles in the water phase and onto interface are obtained, and of which the underlying mechanisms are explained by introducing residual oil. The proposed simulation method provides valuable insights into how nanoparticles adsorb and diffuse onto oil/water interface and how oil/water IFT can be reduced.

Lattice Boltzmann modelling of colloidal suspensions drying in porous media accounting for local nanoparticle effects

A two-dimensional (2-D) double-distribution lattice Boltzmann method (LBM) is implemented to study isothermal drying of a colloidal suspension considering local nanoparticle effects. The two LBMs solve isothermal two-phase flow and nanoparticle transport, respectively. The three local nanoparticle effects on the fluid dynamics considered in this paper are viscosity increase, surface tension drop and local drying rate reduction. The proposed model is first validated by the study of the drying of a 2-D suspended colloidal droplet for two different Péclet numbers, where the evolution of the diameter squared agrees well with experimental results. The model is further validated looking at drying of a colloid in a 2-D capillary tube with two open ends. Compared with experimental results, the best agreement in terms of deposition profile and drying time is obtained when considering all three nanoparticle effects. Afterwards, we apply the model to investigate the complicated drying of a colloidal suspension in a 2-D porous asphalt, considering all three local nanoparticle effects. The drying dynamics, resultant nanoparticle transport, accumulation and deposition are first analysed for a base case. Then a parametric study is conducted varying the initial nanoparticle concentration, porous medium contact angle, nanoparticle contact angle and nanoparticle diffusion coefficient. The influence of these parameters on drying dynamics, drying rate, deposition process and final deposition configurations is analysed in detail, together with the mutual influence of local nanoparticle behaviour. Finally, a unified relation between the average drying rate and the studied parameters is proposed and verified, covering the full parameter ranges of simulations.

Biological heat and mass transport mechanisms behind nanoparticles migration revealed under microCT image guidance

Background and objectivesBlood perfusion, infusion rate, distribution and heating induced redistribution of magnetic nanoparticles inside tumour interstitium governs the heating protocol designs. This study aims to answer three important questions: Why do magnetic nanoparticles redistributes? What causes their migration? Why it is important to be included in priori-treatment planning simulations? Our aim is to test how the regulation of magnetic nanoparticles affects the temperature distribution and how this temperature change modifies tumour microenvironment. We have tested our hypothesis for two cases: (1) when the nanoparticles are lying in close proximity to the flank position of tumour i.e. near the interface of tumour and healthy tissue and (2) when the nanoparticles are located near the skin surface of tumour. Materials and methodsSAS® and MATLAB programs are used to average micro-CT cross-sectional slices containing three-dimensional clusters of pixels corresponds to nanoparticles as a SAR file and Concentration distribution file import to the COMSOL-Multiphysics® 5.2 FEA software for evaluation of temperature distribution and its resulted collateral thermal damage. The volumetric heat generation rate (qMNH‴) is kept ∼ 0.37 W for infusion rate of 4 μL/min. Pennes bioheat equation is three-way coupled with traditional Arrhenius thermal damage model, modified concentration equation in which heat source term (SAR) varies in a directly proportional relationship with Concentration distribution. All variables i.e. Diffusion coefficient, porosity, blood perfusion, metabolic heat generation are varying as a function of thermal damage for a coupled biophysics problem. ResultsThermal signatures of cell-death were evaluated for two case scenarios. The initial distribution volume is 188.46 mm3. On compare and contrast, 6.24% larger thermal diffusion is seen at outer extremities case than at the interface. However, the treatment times are 12.90% (1.13 fold more) to achieve a Ω ≥ 4.6 with ΔT=10°C for latter case. On evaluation of “Source maps” (before heating) with “Destination maps” (after heating) suggests migration of nanoparticles from the regions of higher concentration to the regions of lower concentration due to cell-necrosis induced enhancement in tumour interstitial space. Thermal-diffusion of nanoparticles suggests an increase in redistribution volumes by 23.44% and 26.30% respectively during 99.6% transformation of cancerous cells. This study precisely elucidate qualitative and quantitative aspects of this issue. One of the possible reasons of nanoparticle migration is that the dead cells release intracellular solution after the rupturing of cell membrane. We speculate that five-fold increase in diffusion coefficient of nanoparticles might have played a significant role in particle migration. ConclusionsCNIDC (Cell necrosis induced diffusivity change) and CNIPE (Cell necrosis induced porosity enhancement) may be the two intricate mechanisms that promotes nanoparticles migration.

Enhanced thermal conductivity of nanofluids by introducing Janus particles.

The addition of nanoparticles to a base fluid (i.e., nanofluids) is an effective strategy to achieve a higher thermal conductivity of a fluid. In a common nanofluid, the suspended nanoparticles are mostly symmetrical spheres. In the present paper, we propose to add Janus nanoparticles into a fluid (termed as Janus nanofluids), to further enhance the thermal conductivity of nanofluids. By using molecular dynamics simulations, it is found that the thermal conductivity can be distinctly improved by introducing Janus particles into the nanofluids in contrast with common nanofluids. Based on the calculation results of the molecular radial distribution function around the nanoparticle, and the diffusion coefficient of the base fluid and the Janus nanoparticle, the enhancement in the thermal conductivity of Janus nanofluids is attributed to the enhanced Brownian motion of Janus nanoparticles, which increases the probability of inter-molecular collisions and leads to enhanced energy transfer in nanofluids. The Janus nanofluids proposed in this work provide insights for the design of nanofluids with high thermal conductivity.

Three-dimensional diffusion coefficient measurement by a large depth-of-field rotating point spread function.

A prominent challenge in single-molecule localization microscopy is the real-time, fast, and accurate localization of nano-objects moving in three-dimensional (3D) samples. A well-established method for 3D single-molecule localization is the double-helix pointspread-function (DH-PSF) engineering, which uses additional optical elements to make the PSF exhibit different rotation angles with different nanoparticle depths. However, the compact main lobe size, effective detection depth, and precise conversion between rotation angle and depth are necessary, posing challenges to the DH-PSF generation method. Here we generate a more compact DH-PSF using Fresnel-zone-based spiral phases, and the pure phase mask achieves high transmission efficiency. The final generated DH-PSFs have a linear rotation rate at each axial position, showing a more accurate rotation angle and depth conversion. The Cramer-Rao lower limit calculation results show that the axial depth of DH-PSF extends to ∼11µm with an axial localization precision of ∼45nm at 3000 photons and average background noise of 15. We measured the diffusion coefficient of nanospheres in different concentrations of glycerol using the generated DH-PSF. The measured results are within 6% error from the theoretical values, indicating the superior performance of the DH-PSF for nanoparticle diffusion coefficient measurements.

Collective diffusion of charged nanoparticles in microchannel under electric field

Controllable manipulation of the diffusion of nanoparticles through adopting external fields plays an important role in both separation and delivery of nanoparticles. This work demonstrates that external electric field can effectively enhance or suppress the collective diffusion of nanoparticles in microchannel. Collective diffusion coefficient of nanoparticles under positive or negative electric field was found to be 1.22 or 0.74 times that of the molecular collective diffusion coefficient without electric field applied, respectively. For the case of molecular collective diffusion, the collective diffusion coefficient is 5 times that of the self-diffusion coefficient. The deviation is attributed to the interparticle interactions among the multiple nanoparticles. Findings in this work can improve the understanding of readers for the collective diffusion of nanoparticles driven by concentration gradient under electric field. The phenomenon has great potential in the applications of separation and delivery of charged nanoparticles.

Nanoparticle diffusion in polymer melts in the presence of weak nanoparticle-monomer attractive interactions: A mode-coupling theory study.

Mode-coupling theory is developed and employed to compute the nanoparticle diffusion coefficient in polymer solutions. Theoretical results are compared with molecular dynamics simulation data for a similar model. The theory properly reproduces the simulated effects of the nanoparticle size, mass, and concentration on the nanoparticle diffusion coefficient. Within the mode-coupling theory framework, a microscopic interpretation of the nonmonotonic dependence of the diffusion coefficient on the nanoparticle concentration is given in terms of structural and dynamic effects. Both the size dependence and mass dependence of the diffusion coefficient indicate a pronounced breakdown of the Stokes-Einstein relation for the present model.

Nanoparticle diffusion in polymer melts: Molecular dynamics simulations and mode-coupling theory.

Nanoparticle diffusion in polymer melts is studied by the combination of Molecular Dynamics (MD) simulations and Mode-Coupling Theory (MCT). In accord with earlier experimental, simulation, and theoretical studies, we find that the Stokes-Einstein (SE) hydrodynamic relation Dn ∼ 1/Rn holds when the nanoparticle radius Rn is greater than the polymer gyration radius Rg, while in the opposite regime, the measured nanoparticle diffusion coefficient Dn exceeds the SE value by as much as an order of magnitude. The MCT values of Dn are found to be consistently higher than the MD simulation values. The observed discrepancy is attributed to the approximations involved in constructing the microscopic friction as well as to the approximate forms for dynamic structure factors used in MCT. In a thorough test of underlying MCT assumptions and approximations, various structural and dynamical quantities required as input for MCT are obtained directly from MD simulations. We present the improved MCT approach, which involves splitting of the microscopic time-dependent friction into two terms: binary (originating from short-time dynamics) and collective (due to long-time dynamics). Using MD data as input in MCT, we demonstrate that the total friction is largely dominated by its binary short-time term, which, if neglected, leads to severe overestimation of Dn. As a result, the revised version of MCT, in agreement with the present MD data, predicts 1/Rn 2 scaling of the probe diffusion coefficient in a non-hydrodynamic regime when Rn < Rg. If the total friction is dominated by the collective long-time component, one would observe 1/Rn 3 scaling of Dn in accordance with previous studies.

The influence of inter-particle forces on diffusion at the nanoscale

Van der Waals and electrostatic interactions are the dominant forces acting at the nanoscale and they have been reported to directly influence a range of phenomena including surface adhesion, friction, and colloid stability but their contribution on nanoparticle diffusion dynamics is still not clear. In this study we evaluated experimentally the changes in the diffusion coefficient of nanoparticles as a result of varying the magnitude of Van der Waals and electrostatic forces. We controlled the magnitude of these forces by varying the ionic strength of a salt solution, which has been shown to be a parameter that directly controls the forces, and found by tracking single nanoparticles dispersed in solutions with different salt molarity that the diffusion of nanoparticles increases with the magnitude of the electrostatic forces and Van der Waals forces. Our results demonstrate that these two concurrently dynamic forces play a pivotal role in driving the diffusion process and must be taken into account when considering nanoparticle behaviour.

Mathematical modeling of the heterogeneous distributions of nanomedicines in solid tumors

The distribution of nanomedicines inside solid tumors is often restricted to perivascular areas, leaving most distal tumor cells out of reach. This partly explains modest patient benefit of many nanomedicines compared to their free-form counterparts. The objective for this study is to develop a mathematical model to quantitatively analyze this phenomenon and the influencing factors to such perivascular distribution and seek for effective strategies to alleviate this. A spatial tumor distribution model was firstly constructed to mimic the geometrical structure of tumor vessels and the surrounding tumor cells. This tumor model was further integrated with a systemic pharmacokinetics model for nanoparticles. A variety of factors on the tumor spatial distributions of nanomedicines were considered in the model. With the model, we quantified the effect of these influencing factors on tumor delivery efficacy (ID %), the magnitude of heterogeneous distribution (H index), and the effect of enhanced permeability and retention (EPR). In particularly, we compared the spatial distributions of the nanoparticles and the free payloads insides tumors. The model predicted high degrees of distributional heterogeneity for both nanoparticles and free payloads. The degree of heterogeneity and the influencing factors for free payloads were markedly different from those for nanoparticles. We found that nanoparticle diffusion coefficient was the most effective factor in reducing the nanoparticle H index but exerted moderate influence on the free payloads H index. The most effective factor in reducing the H index of free payload was payload diffusion coefficient. The factors that improved free payload distribution were closely associated with higher drug efficacy. In contrast, the factors that improved nanoparticle spatial distributions did not always confer improved anti-tumor efficacy of the delivered drug. These findings highlight the importance of assessing the heterogeneous free payload distribution in tumors for the development of effective nanomedicines.

Coiled Coil Affinity-Based Systems for the Controlled Release of Biofunctionalized Gold Nanoparticles from Alginate Hydrogels.

Affinity-based systems represent a promising solution to control the delivery of therapeutics using hydrogels. Here, we report a hybrid system that is based on the peptidic E/K coiled coil affinity pair to mediate the release of gold nanoparticles (NPs) from alginate scaffolds. On one hand, the gold NPs were functionalized with the Ecoil-tagged epidermal growth factor (EGF). The bioactivity of the grafted EGF and the bioavailability of the Ecoil moiety were confirmed by EGF receptor phosphorylation assays and by capturing the functionalized NPs on a Kcoil-derivatized surface. On the other hand, alginate chains were modified with azido-homoalanine Kcoil (Aha-Kcoil) by azide-alkyne click chemistry. The hybrid system was formed by dispersing NPs functionalized with the Ecoil-tagged EGF in alginate hydrogels containing either 0, 10, or 20% of Kcoil-modified alginate (Alg-Kcoil). With 20% of Alg-Kcoil, the release of Ecoil-functionalized NPs was reduced by half when compared to the release of NPs without Ecoil, whereas little to no differences were noticed with either 0 or 10% of Alg-Kcoil. Differential dynamic microscopy was used to determine the diffusion coefficient of the NPs, and the results showed a decrease in the diffusion coefficient of Ecoil-functionalized NPs, when compared to bare PEGylated NPs. Altogether, our data demonstrated that the E/K coiled coil system can control the release of NPs in a high Kcoil content alginate gel, opening diverse applications in drug delivery.

Measurement of ultrasound-enhanced diffusion coefficient of nanoparticles in an agarose hydrogel.

An experimental study has been performed to measure the effect of ultrasound on nanoparticle diffusion in an agarose hydrogel. Agarose hydrogel is often used as a simulant for biofilms and certain biological tissues, such as muscle and brain tissue. The work was motivated by recent experiments indicating that ultrasonic excitation of moderate intensity can significantly enhance nanoparticle diffusion in a hydrogel. The objective of the current study was to obtain detailed measurements of the effect of ultrasound on nanoparticle diffusion in comparison to the molecular diffusion in the absence of acoustic excitation. Experiments were conducted with 1 MHz ultrasound waves and nanoparticle diameters of 20 and 100 nm, using fluorescent imaging to measure particle concentration distribution. Under ultrasound exposure, the experiments yield estimates for both acoustic diffusion coefficients as well as acoustic streaming velocity within the hydrogel. Measured values of acoustic streaming velocity were on the order of 0.1 μm/s, which agree well with a theoretical estimate. Measured values of the acoustic diffusion coefficient were found to be 74% larger than the molecular diffusion coefficient of the nanoparticles for 20 nm particles and 133% larger than the molecular diffusion coefficient for 100 nm particles.

Control of viscous fingering by nanoparticles.

A substantial viscosity increase by the addition of a low dose of nanoparticles to the base fluids can well influence the dynamics of viscous fingering. There is a lack of detailed theoretical studies that address the effect of the presence of nanoparticles on unstable miscible displacements. In this study, the impact of nonreactive nanoparticle presence on the stability and subsequent mixing of an originally unstable binary system is examined using linear stability analysis (LSA) and pseudospectral-based direct numerical simulations (DNS). We have parametrized the role of both nondepositing and depositing nanoparticles on the stability of miscible displacements using the developed static and dynamic parametric analyses. Our results show that nanoparticles have the potential to weaken the instabilities of an originally unstable system. Our LSA and DNS results also reveal that nondepositing nanoparticles can be used to fully stabilize an originally unstable front while depositing particles may act as temporary stabilizers whose influence diminishes in the course of time. In addition, we explain the existing inconsistencies concerning the effect of the nanoparticle diffusion coefficient on the dynamics of the system. This study provides a basis for further research on the application of nanoparticles for control of viscosity-driven instabilities.

Comparative Numerical Study of Titanium and Silver Nano-particles Migration from Nano-composite of Polystyrene into Simulants on Experimental Data Basis

Abstract Nano-titanium dioxide and nano-silver combined with polystyrene granules to form a nano-composite film. Migration assess were performed by using food simulants 3% acetic acid (indicative acidic food) and 95% ethanol (indicative fatty food) at 40°C on different times of 2, 4, 6, 8 and 10 days. It was found that nanoparticle migration rate in acidic food was higher than fatty food. Diffusion coefficients of nanoparticles into simulants were estimated by inverse simulation of the migration process using finite-element method and experimental data of varied concentration. Simulation revealed an acceptable consistency between experimental data and predicted values. The numerical results indicated that the greatest diffusion coefficient was obtained by nano-titanium (2.8E-10 to 4.1E-9 m2 s−1) in the 3% acetic acid. Results of concentration distribution confirmed a higher release rate and more uniformed distribution of nanoparticles for nano-titanium in the 3% acetic acid. It also found that in the migration process the diffusion coefficient is more important than the amount of nanoparticles concentration.

Understanding diffusion of intrinsically disordered proteins in polymer solutions: A disorder plus collapse model

Understanding diffusion of intrinsically disordered proteins (IDPs) under crowded environments is of ubiquitous importance to modelling related dynamics in biological systems. In the present work, we proposed a theoretical framework to study the diffusion behavior of IDPs in polymer solutions. IDP is modeled as an ensemble of particles with a wide range of gyration radius subject to Flory-Fisk distribution, where the collapse effect which leads to the shrink of IDP due to polymer crowding is included. The diffusion coefficient of IDP is calculated as the average, denoted by 〈D〉, over the values of the particle samples. By properly incorporating the scaling relations for diffusion coefficient of nanoparticle (NP) in polymer solutions, we are able to evaluate 〈D〉 straightforwardly and reveal the disorder and collapse effects on IDP’s diffusion in an explicit manner. Particular attentions are paid on comparison between the diffusion coefficient of an IDP and that of a NP. Results demonstrate that both disorder and collapse can enhance IDP diffusion rate. Our analysis shows that the crossover behavior reported by experiments can be actually a general phenomenon, namely, while a NP with smaller size than that of an IDP diffuses faster in simple solutions, the IDP may become the faster one under crowded conditions. We apply our theory to analyze the diffusion of several types of IDP in a few different polymer solutions. Good agreements between the theoretical results and the experimental data are obtained.

Diffusion Coefficient of Nanoparticles in Semidilute Polyelectrolyte Solutions Based on Mode Coupling Theory

A theoretical formalism based on mode-coupling theory( MCT) was established to study the longtime diffusion coefficient of nanoparticles in polyelectrolyte solutions. By introducing an approximate summation form for Γpp( k,t),Dmicrocan be calculated straightforwardly and it is necessary to investigate explicitly how D depends on the concentration c of the polymer solution and the nanoparticle size R. For illustration,the theoretical approach is taken to analyze the diffusion of polystyrene nanoparticles in semidilute polyacrylamide solutions which has been studied in detail experimentally. As a result,our theoretical results show very good quantitative agreements with the experimental data in many aspects,such as the strong dependence on c,the large deviation from Stokes-Einstein relation particularly for small particles. Such good agreements clearly demonstrate the validity of our MCT framework,which may serve as a good starting point to study many more complex dynamical behavior associated with polymer solutions.

Photothermal raster image correlation spectroscopy of gold nanoparticles in solution and on live cells.

Raster image correlation spectroscopy (RICS) measures the diffusion of fluorescently labelled molecules from stacks of confocal microscopy images by analysing correlations within the image. RICS enables the observation of a greater and, thus, more representative area of a biological system as compared to other single molecule approaches. Photothermal microscopy of gold nanoparticles allows long-term imaging of the same labelled molecules without photobleaching. Here, we implement RICS analysis on a photothermal microscope. The imaging of single gold nanoparticles at pixel dwell times short enough for RICS (60 μs) with a piezo-driven photothermal heterodyne microscope is demonstrated (photothermal raster image correlation spectroscopy, PhRICS). As a proof of principle, PhRICS is used to measure the diffusion coefficient of gold nanoparticles in glycerol : water solutions. The diffusion coefficients of the nanoparticles measured by PhRICS are consistent with their size, determined by transmission electron microscopy. PhRICS was then used to probe the diffusion speed of gold nanoparticle-labelled fibroblast growth factor 2 (FGF2) bound to heparan sulfate in the pericellular matrix of live fibroblast cells. The data are consistent with previous single nanoparticle tracking studies of the diffusion of FGF2 on these cells. Importantly, the data reveal faster FGF2 movement, previously inaccessible by photothermal tracking, and suggest that inhomogeneity in the distribution of bound FGF2 is dynamic.

MO‐FG‐BRA‐04: Leveraging the Abscopal Effect Via New Design Radiotherapy Biomaterials Loaded with Immune Checkpoint Inhibitors

Purpose:Studies show that stereotactic body radiation therapy (SBRT) of a primary tumor in combination with immune checkpoint inhibitors (ICI) could Result in an immune‐mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However toxicities due to repeated systematic administration of ICI have been shown to be a major obstacle in clinical trials. Towards overcoming these toxicity limitations, we investigate a potential new approach whereby the ICI are administered via sustained in‐situ release from radiotherapy (RT) biomaterials (e.g. fiducials) coated with a polymer containing the ICI.Methods:New design RT biomaterials were prepared by coating commercially available spacers/fiducials with a biocompatible polymer (PLGA) film containing fluorescent nanoparticles of size needed to load the ICI. The release of the nanoparticles was investigated in‐vitro. Meanwhile, an experimentally determined in‐ vivo nanoparticle diffusion coefficient was employed in analytic calculations based on Fick's second law to estimate the time for achieving the concentrations of ICI in the tumor draining lymph node (TDLN) that are needed to engender the abscopal effect during SBRT. The ICI investigated here was anti‐CTLA‐4 antibody (ipilimumab) at approved FDA concentrations.Results:Our in ‐vitro study results showed that RT biomaterials could be designed to achieve burst release of nanoparticles within one day. Meanwhile, our calculations indicate that for a 2 to 4 cm tumor it would take 4–22 days, respectively, following burst release, for the required concentration of ICI nanoparticles to accumulate in the TDLN during SBRT.Conclusion:Current investigations combining RT and immunotherapy involve repeated intravenous administration of ICI leading to significant systemic toxicities. Our preliminary results highlight a potential new approach for sustained in‐situ release of the ICI from new design RT biomaterials. These results provide impetus for more studies to leverage the powerful abscopal effect, while minimizing systemic toxicities through the new approach.

Pericellular matrix plays an active role in retention and cellular uptake of large-sized nanoparticles.

As the outmost coating of cells, the pericellular matrix (PCM) involved in various cellular functions has been exploited previously to be able to accumulate 120 nm Au nanoparticles (NPs), adjust their diffusion coefficient similar to that of membrane receptors, and enhance their uptake efficiency. In this study, the interactions between PCM and NPs with different sizes and materials were systematically investigated. We found that PCM can selectively enhance the retention and cellular uptake of NPs with diameters from 50 to 180 nm, but has no enhancement effect for 20 nm NPs. Identical behaviors of PCM was observed for both Au NPs and polystyrene NPs, indicating that this unique phenomenon is more related to the dimensions of the NPs. The study of single-particle tracking of 50-180 nm NPs on the surface of thick PCM cells revealed that PCM actively adjusts the diffusion coefficient of NPs to ∼0.1 μm(2)/s regardless of their sizes. By blocking the receptor-mediated endocytosis (RME) pathway with four different inhibitors, this active role of PCM can be effectively suppressed, further confirming that the trapping and retention of NPs by PCM is an inherent biological function. These findings provided new insights for better understanding of the RME pathway and may have promising NP-based applications for controlled drug delivery and therapy in biomedicine.