Aggregation Of Magnetic Nanoparticles Research Articles

Self-assembled electroactive MOF–magnetic dispersible aptasensor enables ultrasensitive microcystin-LR detection in eutrophic water

There is a high demand for developing accurate and sensitive microcystin-LR (MC-LR) analysis methods in complex environmental water due to its serious damage to human health. Herein, a self-assembled electroactive MOF–magnetic dispersible aptasensor has been developed to enable ultrasensitive MC-LR detection both in laboratory and in eutrophic water. Through the analyte-induced unwinding of an aptamer sequence-contained hairpin DNA on the surface of Zr-MOF electrochemical tag, the released chain-end can be easily found by the dispersible magnetic nanoparticles. Then the external magnet facilitated the aggregation of magnetic nanoparticles with captured MOF tags to the sensing surface. Thus, a highly sensitive self-assembled dispersible aptasensor for determination of MC-LR in environmental water samples without preconcentration was constructed. It was able to detect MC-LR from 0.005 to 100 ng mL−1, and was also employed successfully for MC-LR quantification in water samples from Lake Taihu, exhibiting a great potential for monitoring pollutants.

Aggregation of magnetic nanoparticles functionalized with trans-resveratrol in aqueous solution

In the framework of a protein–ligand-fishing strategy to identify proteins that bind to trans-resveratrol, a natural phenolic compound with pharmacological benefits, we have developed magnetic nanoparticles covalently linked to trans-resveratrol through three different derivatives and examined their aggregation behavior in aqueous solution. The monodispersed magnetic core (18 nm diameter) with its mesoporous silica shell (93 nm diameter) exhibited a notable superparamagnetic behavior useful for magnetic bioseparation. The hydrodynamic diameter, deduced from dynamic light scattering analysis, of the nanoparticle increased from 100 to 800 nm when the aqueous buffer changed from pH 10.0–3.0. A size polydispersion occurred from pH 7.0–3.0. In parallel, the value of the extinction cross section increased according to a negative power law of the UV wavelength. This was mainly due to light scattering by mesoporous silica, whereas the absorbance cross section remained very low in the 230–400 nm domain. The three types of resveratrol-grafted magnetic nanoparticles exhibited similar scattering properties, but their absorbance spectrum was consistent with the presence of trans-resveratrol. Their functionalization increased their negative zeta potential when pH increased from 3.0 to 10.0. The mesoporous nanoparticles were monodispersed in alkaline conditions, where their anionic surface strongly repulsed each other but aggregated progressively under van der Waals forces and hydrogen bonding when negative zeta potential decreased. The characterized results of nanoparticle behavior in aqueous solution provide critical insight for further study of nanoparticles with proteins in biological environment.

Enzyme-Triggered Transforming of Assembly Peptide-Modified Magnetic Resonance-Tuned Probe for Highly Sensitive Imaging of Bacterial Infection In Vivo.

Confirming bacterial infection at an early stage and distinguishing between sterile inflammation and bacterial infection is still highly needed for efficient treatment. Here, in situhighly sensitive magnetic resonance imaging (MRI) bacterial infection in vivobased on a peptide-modified magnetic resonance tuning (MRET) probe (MPD-1) that responds to matrix metallopeptidase 2 (MMP-2) highly expressed in bacteria-infected microenvironments is achieved. MPD-1 is an assembly of magnetic nanoparticle (MNP) bearing with gadolinium ion (Gd3+ ) modified MMP-2-cleavable self-assembled peptide (P1 ) and bacteria-targeting peptide (P), and it shows T2 -weighted signal due to the assemble of MNP and MRET ON phenomenon between MNP assembly and Gd3+ . Once MPD-1 accumulates at the bacterially infected site, P1 included in MPD-1 iscleaved explicitly by MMP-2, which triggers the T2 contrast agent of MPD-1 to disassemble into the monomer of MNP, leading the recovery of T1 -weighted signal. Simultaneously, Gd3+ detaches from MNP, further enhancing the T1 -weighted signal due to MRET OFF. The sensitive MRI of Staphylococcus aureus (low to 104 CFU) at the myositis site and accurate differentiation between sterile inflammation and bacterial infection based on the proposed MPD-1 probe suggests that this novel probe would be a promising candidate for efficiently detecting bacterial infection in vivo.

Win-Win Cooperation: Magnetic relaxation switching biosensor for chloramphenicol detection based on the pipet platform and antigen-driven enzyme-free dual signal amplification strategy

Herein, we developed an enzyme-free dual signal amplification magnetic relaxation switching biosensor to detect the high hazard chloramphenicol based on the significant advantages of the pipet platform (low cost and easy operation). The competitive immunoassay was carried out by coating the polydopamine-modified pipets with the antibody, causing a content change of trigger DNA-chloramphenicol-antigen conjugate (the first signal amplification) in the supernatant. This triggered the aggregation of magnetic nanoparticles with three-dimensional DNA network structures (the second signal amplification) for chloramphenicol quantitative analysis by changes in transverse relaxation time (T2). The pipet platform can simplify the sample pretreatment process to eliminate the potential interference with magnetic probes. Its low-cost combined with the enzyme-free strategy greatly reduces the overall detection expenses. The antigen-driven dual signal amplification strategy not only has high sensitivity (1.37 pg/mL), but also provides an alternative path for the efficient combination of immunoassay and DNA signal amplification.

Thermographical Method to Assess the Performance of Magnetic Nanoparticles in Hyperthermia Experiments through Spatiotemporal Temperature Profiles

The evaluation of the specific power absorption of magnetic nanoparticles (MNPs) for magnetic hyperthermia (MH) applications has been performed through either local temperature probing or magnetic measurements so far. Each of these methods has advantages and drawbacks, and the concurrent use of both techniques offers the most reliable results. In this work, we propose an alternative strategy based on thermographic images to obtain two-dimensional temperature maps that allow the determination of the power absorption and other relevant thermodynamic parameters in MH experiments in a noninvasive way. This procedure and analysis are convenient to determine the heating performance of MNPs under the viscous conditions of in vitro and in vivo assays and to follow the time evolution of the temperature spatial distribution in the sample simultaneously. For this purpose, iron-oxide MNPs with 25-nm average diameter are coated with glucose and dispersed into different 8% polyacrylamide gels, which serve as phantoms that emulate intracellular viscosity. Power absorption experiments are performed under ac magnetic fields ($H=$ 32 kA/m; $f=$ 350 kHz) and the temperature evolution of the sample is monitored through a commercial thermographic camera (resolution, $240\ifmmode\times\else\texttimes\fi{}180$ pixels; temperature accuracy, 2 K). To complement this simple setup, we design a program consisting of a detailed procedure for extracting graphical information from the video frames and obtaining spatiotemporal temperature profiles. The analysis of these profiles allows us to gather information on temperature, energy, power, and heat flux during the MH experiments. This method and analysis allows us to identify spatial inhomogeneities in samples, such as different local MNP density, which is extremely useful for the development of the therapy in vitro and the application in vivo where MNP aggregation is often present.

Monitoring magnetic nanoparticle clustering and immobilization with thermal noise magnetometry using optically pumped magnetometers.

Thermal noise magnetometry (TNM) is a recently developed magnetic characterization technique where thermally induced fluctuations in magnetization are measured to gain insight into nanomagnetic structures like magnetic nanoparticles (MNPs). Due to the stochastic nature of the method, its signal amplitude scales with the square of the volume of the individual fluctuators, which makes the method therefore extra attractive to study MNP clustering and aggregation processes. Until now, TNM signals have exclusively been detected by using a superconducting quantum interference device (SQUID) sensor. In contrast, we present here a tabletop setup using optically pumped magnetometers (OPMs) in a compact magnetic shield, as a flexible alternative. The agreement between results obtained with both measurement systems is shown for different commercially available MNP samples. We argue that the OPM setup with low complexity complements the SQUID setup with high sensitivity and bandwidth. Furthermore, the OPM tabletop setup is well suited to monitor aggregation processes because of its excellent sensitivity in lower frequencies. As a proof of concept, we show the changes in the noise spectrum for three different MNP immobilization and clustering processes. From our results, we conclude that the tabletop setup offers a flexible and widely adoptable measurement unit to monitor the immobilization, aggregation, and clustering of MNPs for different applications, including interactions of the particles with biological systems and the long-term stability of magnetic samples.

Plasmonic/magnetic liposomes based on nanoparticles with multicore-shell architecture for chemo/thermotherapy

Multifunctional nanosystems are capable to carry one or more therapeutic agents (thermal and/or targeting agents and chemotherapeutic drugs), offering the capability to concurrently perform different treatment modalities using a single nanosystem. Cluster nanostructures, consisting of densely packed aggregates of magnetic nanoparticles, have shown enhanced heating capabilities. Their combination with plasmonic nanoparticles enable synergistic behavior between dual hyperthermia (magneto-photothermia), allowing overheating cancer cells while increasing drug toxicity. In this work, multicore magnetic nanoparticles (NPs) of MnFe2O4 were prepared using oxamide and melamine as clustering agents. The multicore NPs prepared with oxamide were covered with a gold shell, resulting in multicore magnetic/plasmonic NPs with an increased SAR of 173.80 W/g, under NIR light. Liposomes based on these magnetic/plasmonic NPs were prepared and the model drug curcumin was loaded in these nanocarriers with a high encapsulation efficiency. The fusion between the curcumin-loaded magnetic/plasmonic liposomes and models of cell membranes (labelled with Nile Red) was confirmed by FRET, pointing the magneto/plasmonic liposomes as promising for dual cancer therapy (combined hyperthermia and chemotherapy).

Nanostructured Assembly of Magnetic and Plasmonic Nanoparticles Transferred from AOT Winsor Phases to Oil‐in‐Water Functional Dispersions

AbstractNanoparticle interactions can mediate assemblies and self‐organization into colloidal superstructures, if then control of the size and stabilization is highly required towards the fabrication of functional nanomaterials. In the proposed approach, different types of water‐dispersible and oil‐dispersible nanoparticles were incorporated in water‐in oil (w/o) microemulsions stabilized by Aerosol‐OT (AOT) as surfactant. Phase separation at higher surfactant and water contents resulted in the formation of a heterocoagulate, which can be separated with an external magnet. This magnetic heterocoagulate, which can contain 3 different types of nanoparticles, can be dispersed in longer‐chain carboxylic acids. An additional phase‐transfer into oil‐in water (o/w) dispersions was mediated by an auxiliary surfactant in water‐ethanol. The resulting nanostructures from heterocoagulates formed at higher temperatures consisted on inner domains of water‐dispersible nanoparticles embedded in a matrix‐shell of oleyl‐capped nanoparticles. Thus, a new encapsulation strategy is achieved under relative mild conditions, combining three types of nanoparticles and providing compartmentalization and magnetic‐responsiveness.

Naked-eye detection of antibiotic resistance gene sul1 based on aggregation of magnetic nanoparticles and DNA amplification products

The continued spread of antimicrobial resistance is a global problem. In fact, the WHO has declared antimicrobial resistance one of the top 10 global public health threats facing humanity. Molecular methods offer a faster means of characterizing resistant strains than phenotypic drug susceptibility testing. We have developed a molecular detection method that generates visible aggregates from DNA amplified products and functionalized magnetic nanoparticles. The amplification and detection procedure take less than 2 h. In this study we also investigated the factors behind the aggregation and confirmed that the size of the padlock probe is a relevant parameter for the amplification efficiency. We compared a 92 and a 69 nt long padlock probe and found the latter to perform over 4 times better than the 92 nt padlock probe. This effect was related to a higher quantity of amplification products produced by the shorter padlock probe. Consequently, the quantity of amplified DNA products affects the aggregation in a positive way, and thanks to it, a better assay sensitivity was achieved. Finally, using our developed method, we could detect as little as 1 amol of the antibiotic-resistance gene sul1 from a sample containing a multiresistance plasmid. We were also able to quantify the amount of plasmid DNA through absorbance spectroscopy and AC susceptometry. The presented results form the foundation of future development of an ultrasensitive and cheap detection approach that could be used in point of care settings.

Effects of major guidance parameters on aggregated magnetic particles during magnetic drug targeting

Utilization of the aggregation phenomenon in magnetic nanoparticles (MNPs) under a magnetic field has been considered as an efficient mechanism to overcome the lack of actuation force and low imaging resolution for succesuful magnetic drug targeting (MDT). In previous studies, it is assumed that during MDT the aggregation happens in the chain shapes and they are in an equilibrium state and further aggregations do not occur. However, in reality, aggregated magnetic particles are in a non-equilibrium state due to the effects of blood flow and the time-varying magnetic field. As a result, further aggregation can occur. If the repeated aggregation of MNPs in the non-equilibrium state is not considered, it can cause the sticking and clogging phenomena inside the blood vessel, which can significantly affect targeting performance of MDT and raise the safety concerns about the method. Therefore, major paramters of the aggregated magnetic particles should be clearly examined under non-equilibrium state during MDT. Duing MDT, magnetic particle chains with individually different volumes can experience different magnetic field, magnetic field gradient, and flow rate. Therefore, in this paper, we have analyzed four main paramters that can influence the MDT, including chain length, magnetic field, magnetic field gradient, and flow rate. Finally, we have developed a MDT simulator to observe the aggregation phenomenon of magnetic particles and their targeting performance during steering in a Y-channel vessel using an intutive user interface. The results show that aggregation volume and targeting performance can be controlled by modulating the external magnetic field and magnetic field gradient. The proposed aggregation guidance studies can provide insightful guidelines for determining a magnetic drug targeting scheme.

Hybrid Ni–Co–Ni Structures Prepared by Magnetophoresis as Efficient Permanent Magnets for Integration into Microelectromechanical Systems

The direct integration of performant permanent magnets (PMs) within miniaturized circuits remains both a scientific and a technological challenge. Magnetophoresis‐driven capillary assembly of hard magnetic nanoparticles is a promising approach to fabricate 3D rare‐earth‐free PMs. However, this process implies the use of soft magnetic blocks to generate the magnetic field gradients required to localize the assembly directly onto silicon substrates. The impact of these soft elements onto the overall magnetic properties is evaluated using Co nanorods as hard material and 150 μm–thick Ni blocks. As expected, the presence of Ni softens the overall properties of the hybrid magnet obtained, but PM properties are preserved for reduced Ni volumes. Magnetic induction as high as 19 mT at a distance of 200 μm is generated by the hybrid Ni–Co–Ni structures, allowing for the electromagnetic actuation of a microelectromechanical resonant sensor.

M13 bacteriophage as biometric component for orderly assembly of dynamic light scattering immunosensor

The ordered assembly of nanostructure is an effective strategy used to manipulate the hydrodynamic diameter (DH) of nanoparticles. Herein, a versatile dynamic light scattering (DLS) immunosensing platform is presented to sensitively detect small molecules and biomacromolecules by using the M13 phage as the building module to order the assembly of gold nanoflowers and gold-coated magnetic nanoparticles, respectively. After the directional assembly of M13 phage, the DH of the probes was significantly increased due to its larger filamentous structure, thus improving the detection sensitivity of the DLS immunosensor. The designed M13 assembled DLS immunosensor with competitive and sandwich formats showed high sensitivities for ochratoxin A and alpha-fetoprotein in real corn and undiluted serum samples, with the detection limits of 1.37 and 57 pg/mL, respectively. These values are approximately 15.8 and 164.9 times lower than those of traditional phage-based enzyme-linked immunosorbent assays. Collectively, this work provides a promising strategy to manipulate the DH of nanoparticles by highly evolved biomaterials such as engineered M13 phages and opens upon a new direction for developing DLS immunosensors to detect various targets by the fusion expression of special peptide or nanobody on the pIII or pVIII protein of M13 phage.

Electric field-induced assembly of magnetic nanoparticles from dielectric ferrofluids on planar interface

Electric fields, similar to magnetic fields, could be the driving force inducing the assembling of magnetic nanoparticles at the interface. Using specular neutron reflectometry, the assembly of superparamagnetic nanoparticles of a dilute classical ferrofluid (magnetite coated with oleic acid in transformer oil) on the planar surface of a metal electrode (copper) was observed when an out-of-plane electric field was applied to the interface. Starting only from the wetting layer of magnetic nanoparticles on the electrode surface in the absence of an electric field, the evolution of the interface structure with an increase in the electric field strength is traced by analyzing changes in the scattering length density depth profiles derived from neutron reflectivity curves. At a sufficiently strong electric field, a second adsorption layer is revealed, which becomes even more saturated than the initial one. The cause of the observed effects is related to the polarization of the particles in the electric field and their interaction as dipoles. Relaxation measurements (after the field is switched off) prove that the local electric field induced by strongly interacting electric dipoles in concentrated adsorption layers is an important feature determining the enhancement of adsorption of nanoparticles.

Methods of investigating the demagnetization factors within assemblies of superparamagnetic nanoparticles

Three-dimensional distributions of demagnetization factors Nd within assemblies of magnetic nanoparticles have been investigated along the axes of cuboid containing vessels. From the results of a numerical polar-based model, a significant skew toward high values in the number distribution is observed and often overlooked by the assumed uniformity of the conventional analytical approach. To enable comparison with experiment, new transverse susceptibility techniques have been developed, which are also applicable to superparamagnetic assemblies that do not have the magnetization features normally required using conventional methods. Applying the two techniques to a system of ∼13 nm magnetite (Fe3O4) particles resulted in the difference between the in-plane and out-of-plane Nd factors of (0.21 ± 0.03) and (0.201 ± 0.009), respectively, which shows closest agreement with the simulation value for the mode of (0.19 ± 0.02). The median and mean results of the model move further away from the experimental result, yielding values of (0.17 ± 0.02) and (0.16 ± 0.02), respectively, which is consistent with the skewed distributions observed here. In all cases, the sum of the Nd factors from each orthogonal axis was equal to 1, giving further confidence in the model. The new methods allow measurements on the superparamagnetic systems often found at this scale, and the agreement with the model means that the spatial distribution of Nd factors may now be taken into account in studies on any nanoscale material that considers the whole structure as a distribution of magnetic elements.

Effect of the distribution of anisotropy constants on the magnetic properties of iron oxide nanoparticles

The distribution of shape anisotropy constants in two colloids of iron oxide nanoparticles has been measured from the distribution of particle elongations within each system. The results are in good agreement with the values calculated from a temperature decay of remanence measurement. For a fluid with a saturation magnetisation of 420 emu/cc and an average particle elongation of ∼ 1.3, the distribution of energy barriers is controlled by both the distribution of particle sizes and particle elongations. For a fluid with a saturation magnetisation of 320 emu/cc and a wide distribution of particle sizes, the energy barrier to reversal can be assumed to be controlled by the distribution of particle volumes. These results highlight the need to take into account the distribution of anisotropy constants when making predictions of the heating properties of assemblies of magnetic nanoparticles for hyperthermia applications.

Directed Assembly of Magnetic Nanoparticles into Centimeter Scale Wires for a 3D Cell Culture Platform

Directed Assembly of Magnetic Nanoparticles into Centimeter Scale Wires for a 3D Cell Culture Platform

Computational methodology for drug delivery to the inner ear using magnetic nanoparticle aggregates

Background and objective: The main goal of the proposed study is to improve the efficiency of the ear treatment via targeted drug delivery to the inner ear, i.e. the cochlea. Although pharmacotherapy has been proposed as a solution to prevent damage or restore functionality to hair cells, the main challenge in such treatments is ensuring adequate drug delivery to the cells. To this end, we present a methodology for the evaluation of the magnetic forces needed to move magnetic particle nanorobots (abbreviated as MNP) and their aggregates through the cochlea round window membrane (RWM).Methods: The FEM - Lagrangian-Eulerian approach (Abaqus software) was used to determine the specific parameters of movement of the nanoparticles crossing the RWM. This method results in a high consistency of FEM simulations and in-vivo experimental results in regards to the required magnetic force during the movement of spherical nanoparticles with a given viscosity ηave. Based on the analysis of the experimental studies found in subject literature, the sizes of the MNPs and their aggregates able to cross RWM with and without the application of magnetic force FM have been determined.Results: The present work accounts for both the experimental and theoretical aspects of these investigations. Presented research confirms the definite usability of the Lagrange-Euler method for the precise determination of the required magnetic force value FM to control the accelerated motion of MNP aggregates of complex shapes through RWM. It is possible to determine the predominant parameters with a precision of less than 5% for single-layer aggregates and spatial aggregates crossing the RWM. It can be concluded that the MNPs and their aggregates should not be larger than 500–750 nm to cross the RWM with high velocities of penetration close to 800 nm/s for magnetic forces of hundreds 10−14 Newtons.Conclusions: The proposed Lagrangian-Eulerian approach is capable of accurately predicting the movement parameters of MNP aggregates of irregular shape that are close to the experimental test cases. The presented method can serve as a supplementary tool for the design of drug delivery systems to the inner ear using MNPs.

Parallel Multichannel Assessment of Rotationally Manipulated Magnetic Nanoparticles.

BackgroundRotational manipulation of chains or clusters of magnetic nanoparticles (MNPs) offers a means for directed translation and payload delivery that should be explored for clinical use. Multiple MNP types are available, yet few studies have performed side-by-side comparisons to evaluate characteristics such as velocity, movement at a distance, and capacity for drug conveyance or dispersion.PurposeOur goal was to design, build, and study an electric device allowing simultaneous, multichannel testing (e.g., racing) of MNPs in response to a rotating magnetic field. We would then select the “best” MNP and use it with optimized device settings, to transport an unbound therapeutic agent.MethodsA magnetomotive system was constructed, with a Helmholtz pair of coils on either side of a single perpendicular coil, on top of which was placed an acrylic tray having multiple parallel lanes. Five different MNPs were tested: graphene-coated cobalt MNPs (TurboBeads™), nickel nanorods, gold-iron alloy MNPs, gold-coated Fe3O4 MNPs, and uncoated Fe3O4 MNPs. Velocities were determined in response to varying magnetic field frequencies (5–200 Hz) and heights (0–18 cm). Velocities were normalized to account for minor lane differences. Doxorubicin was chosen as the therapeutic agent, assayed using a CLARIOstar Plus microplate reader.ResultsThe MMS generated a maximal MNP velocity of 0.9 cm/s. All MNPs encountered a “critical” frequency at 20–30 Hz. Nickel nanorods had the optimal response based on tray height and were then shown to enable unbound doxorubicin dispersion along 10.5 cm in <30 sec.ConclusionA rotating magnetic field can be conveniently generated using a three-coil electromagnetic device, and used to induce rotational and translational movement of MNP aggregates over mesoscale distances. The responses of various MNPs can be compared side-by-side using multichannel acrylic trays to assess suitability for drug delivery, highlighting their potential for further in vivo applications.

Aspects of Uniform Horizontal Magnetic Field and Nanoparticle Aggregation in the Flow of Nanofluid with Melting Heat Transfer.

The current exploration focuses on the impact of homogeneous and heterogeneous chemical reactions on titanium dioxide-ethylene glycol (EG)-based nanoliquid flow over a rotating disk with thermal radiation. In this paper, a horizontal uniform magnetic field is used to regularise the flow field produced by a rotating disk. Further, we conduct a comparative study on fluid flow with and without aggregation. Suitable transformations are used to convert the governing partial differential equations (PDEs) into ordinary differential equations (ODEs). Later, the attained system is solved numerically by means of the shooting method in conjunction with the Runge–Kutta–Fehlberg fourth-fifth-order method (RKF-45). The outcome reveals that the fluid flow without nanoparticle aggregation shows enhanced heat transport than for augmented values of melting parameter. Furthermore, for augmented values of strength of homogeneous and heterogeneous reaction parameters, the mass transfer is greater in fluid flow with aggregation conditions.

Manipulating Nanoparticle Aggregates Regulates Receptor-Ligand Binding in Macrophages.

The receptor-ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor magnetic nanoparticle aggregates of tunable sizes over the cell-adhesive RGD ligand (Arg-Gly-Asp)-active material surface while maintaining the density of dispersed ligands accessible to macrophages at constant. Lowering the accessible ligand dispersity by increasing the aggregate size at constant accessible ligand density facilitates the binding of integrin receptors to the accessible ligands, which promotes the adhesion of macrophages. In high ligand dispersity, distant magnetic manipulation to lift the aggregates (which increases ligand accessibility) stimulates the binding of integrin receptors to the accessible ligands available under the aggregates to augment macrophage adhesion-mediated pro-healing polarization both in vitro and in vivo. In low ligand dispersity, distant control to drop the aggregates (which decreases ligand accessibility) repels integrin receptors away from the aggregates, thereby suppressing integrin receptor-ligand binding and macrophage adhesion, which promotes inflammatory polarization. Here, we present "accessible ligand dispersity" as a novel fundamental parameter that regulates receptor-ligand binding, which can be reversibly manipulated by increasing and decreasing the ligand accessibility. Limitless tuning of nanoparticle aggregate dimensions and morphology can offer further insight into the regulation of receptor-ligand binding in host cells.