Change In Size Of Nanoparticles Research Articles

Compact lab-on-printed circuit board (PCB) for free-surfactant silver nanomaterial synthesis

This study introduces a compact Lab-on-Printed Circuit Board (PCB) device featuring thermal integrated microfluidic channels designed for nanoparticle synthesis. Commonly, complex heating chambers are employed to expedite reactions and enhance nanomaterial productivity, yet they pose challenges in temperature control and mixing rates within the reaction chamber. To address these issues, we propose a compact device composed of PDMS microfluidic channels and a PCB platform. The PCB heater, constructed to precisely regulate temperature within the microfluidic channels, utilizes copper lines as heating resistors, while an Arduino kit is employed for temperature measurement and control. Leveraging a Proportional–integral–derivative (PID) controller through programming, the device achieves rapid temperature increase and stable control within the microfluidic channels. Experimental validation demonstrates the operational principles and capabilities of this device, showcasing observable changes in nanoparticle size and morphology. Discussions on these observed results are included in this work.

Nanoparticle Isolation from Biological Media for Protein Corona Analysis: The Impact of Incubation and Recovery Protocols on Nanoparticle Properties

Nanoparticles are increasingly implemented in biomedical applications, including the diagnosis and treatment of disease. When exposed to complex biological media, nanoparticles spontaneously interact with their surrounding environment, leading to the surface-adsorption of small and bio- macromolecules- termed the “corona”. Corona composition is governed by nanoparticle properties and incubation parameters. While the focus of most studies is on the protein signature of the nanoparticle corona, the impact of experimental protocols on nanoparticle size in the presence of complex biological media, and the impact of nanoparticle recovery from biological media has not yet been reported. Here using a non-degradable robust model, we show how centrifugation-resuspension protocols used for the isolation of nanoparticles from incubation media, incubation duration and shear flow conditions alter nanoparticle parameters including particle size, zeta potential and total protein content.Our results show significant changes in nanoparticle size following exposure to media containing protein under different flow conditions, which also altered the composition of surface-adsorbed proteins profiled by SDS-PAGE. Our in situ analysis of nanoparticle size in media containing protein using particle tracking analysis highlights that centrifugation-resuspension is disruptive to agglomerates that are spontaneously formed in protein containing media, highlighting the need for in situ analytical methods that do not alter the intermediates formed following nanoparticle exposure to biological media.Nanomedicines are mostly intended for parenteral administration, and our findings show that parameters such as shear flow can significantly alter nanoparticle physicochemical parameters. Overall, we show that the centrifugation-resuspension isolation of nanoparticles from media significantly alters particle parameters in addition to the overall protein composition of surface-adsorbed proteins. We recommend that nanoparticle characterization pipelines studying bio-nano interactions during early nanomedicine development consider biologically-relevant shear flow conditions and media composition that can significantly alter particle physical parameters and subsequent conclusions from these studies.

Preparation of Solid Lipid Nanoparticles of Cinnamaldehyde and Determination of Sustained Release Capacity.

Natural plant essential oils cannot be applied on a large scale due to their high volatility, easy deactivation, etc. This study provides a new method to prepare a long-lasting, slow-release essential oil product by taking advantage of solid lipid nanoparticles, which will provide a scientific guideline for the future essential oil industry. In this article, solid lipid cinnamaldehyde nanoparticles were prepared using an ultrahigh-pressure homogenization method. SLN-CA with a particle size of 74 ± 5 nm, PDI of 0.153 ± 0.032, and zeta potential of -44.36 ± 2.2 mV was screened using an additional amount of cinnamaldehyde, the ratio of oil phase components, and the homogenization pressure and number of times as factors. Differential thermal analysis and spectroscopy demonstrated that cinnamaldehyde was successfully encapsulated inside the nanoparticles. The change in particle size of nanoparticles under different conditions and times was used as an indicator of stability. The stability of the finished nanoparticles was evaluated. The retention and slow-release ability of cinnamaldehyde were investigated using the concentration of cinnamaldehyde in nanoparticles as an indicator. The results showed that after 15 days, SLN-CA retained 52.36% of the concentration from 15 days prior. The bacterial inhibition test shows that SLN-CA can inhibit bacteria.

Electrical Mobility as an Indicator for Flexibly Deducing the Kinetics of Nanoparticle Evaporation.

Condensation and evaporation of vapor species on nanoparticle surfaces drive the aerosol evolution in various industrial/atmospheric systems, but probing these transient processes is challenging due to related time and length scales. Herein, we present a novel methodology for deducing nanoparticle evaporation kinetics using electrical mobility as a natural size indicator. Monodispersed nanoparticles are fed to a differential mobility analyzer which serves simultaneously as an evaporation flowtube and an instrument for measuring the electrical mobility, realizing measurements of evaporation processes with time scales comparable to the instrument response time. A theoretical framework is derived for deducing the evaporation kinetics from instrument responses through analyzing the nanoparticle trajectory and size–mobility relationship, which considers the coupled mass and heat transfer effect and is applicable to the whole Knudsen number range. The methodology is demonstrated against evaporation but can potentially be extended to condensation and other industrial/atmospheric processes involving rapid size change of nanoparticles.

Identification of Nanoscale Processes Associated with the Disorder-to-Order Transformation of Carbon-Supported Alloy Nanoparticles.

Due to their ordered crystal structures and high structural stabilities, intermetallic nanoparticles often display enhanced catalytic, magnetic, and optical properties compared to their random alloy counterparts. Intermetallic nanoparticles can be achieved by thermal annealing of their disordered (random alloy) counterparts. However, high temperatures and long annealing times needed to achieve the disorder-to-order transition often lead to a loss of sample monodispersity and an increase in the average size of nanoparticles. Here, we performed ex situ powder X-ray diffraction (XRD) and in situ annealing transmission electron microscopy (TEM) experiments to elucidate nanoscale processes that contribute to the ordering of carbon-supported PdCu nanoparticles as a model system. Random alloy PdCu nanoparticles supported on carbon were thermally annealed for various lengths of time at the disorder-to-order phase transition temperature, where changes in nanoparticle size and the crystal phase were monitored. The nanoparticles were only completely transformed to the intermetallic phase by undertaking measures to deliberately increase their size by increasing the number of nanoparticles on the carbon support. In situ annealing TEM experiments reveal nanoscale processes that account for the disorder-to-order phase transformation. Five different processes were observed at 400 °C. Isolated nanoparticles remained in the random alloy phase or underwent a phase transformation to the intermetallic phase. Nanoparticles fused with neighboring nanoparticles resulting in no change in phase or conversion to the intermetallic phase. Evidence of vapor transport was also observed, as some isolated nanoparticles were found to diminish in size upon heating. These variable processes account for the heterogeneity often observed for intermetallic nanoparticle samples achieved through annealing and motivate the development of synthetic routes that suppress particle-particle coalescence, as well as investigating metal-support interactions to facilitate the disorder-to-order phase transformation under mild conditions. Overall, this work furthers our knowledge of the formation of intermetallic nanoparticles by thermal annealing approaches, which could accelerate the development of electrocatalysts and the application of intermetallic nanoparticles in magnetic storage devices.

Development of novel poly-l-lysine-modified sericin-coated superparamagnetic iron oxide nanoparticles as siRNA carrier

Small interfering RNA (siRNA) is a promising therapeutic modality, however, its successful clinical application is still challenging due to the lack of safe and efficient carrier systems. Superparamagnetic iron oxide nanoparticles (SPIONs)-based drug or gene carrier systems have displayed tremendous promise in nanomedicine. They possess intrinsic unique superparamagnetism that provides them to be concentrated in the targeted therapeutic site of action where an external magnetic field is applied. SPIONs can be also designed as theranostic agents to achieve simultaneous therapeutic and diagnostic purposes. Despite these favorable features, SPIONs are colloidally unstable and can be easily eliminated in the circulation. More importantly, the toxicological concerns associated with SPIONs, which often lead to the generation of reactive oxygen species (ROS), need to be thoroughly considered. Various types of polymers have been proposed so far to cover the surface of SPION to overcome these disadvantages. Silk protein, sericin can be ideal as a coating material due to its high biocompatibility, good biodegradability, and in vivo stability. In terms of the development of SPIONs as siRNA carriers, to the best of our knowledge, no protein was used as the coating material, and SPIONs coated with sericin have not been reported in the literature as a drug or gene carrier system. The present study aimed to design and develop a novel siRNA carrier system based on SPIONs. We prepared and characterized a nanomaterial comprised of SPIONs covalently coated with a biocompatible protein, sericin (Ser), and modified with a cationic polymer, poly- l -lysine (PLL) to incorporate the negatively charged siRNA. Transmission electron microscopy (TEM) images revealed that obtained nanoparticles had narrow size distribution with spherical shape and coated nanoparticles presented black spheres in the SPION core surrounded with a gray layer, which indicated sericin coating. Adding PLL to Ser-SPIONs did not cause any dramatic change in nanoparticle size whereas it provided a net positive charge to the particles. Additionally, electron spin resonance (ESR) analysis showed that sericin coating and PLL modification did not efface the superparamagnetic properties of the particles. We successfully attached the control-siRNAs to the surface of PLL/Ser-SPIONs, forming siRNA-PLL/Ser-SPION nanoplatforms and achieving high siRNA binding efficiencies ranged between 81.90% and 93.50%. The ability of SPIONs-based nanocarriers to fulfill their promises in clinical use depends on keeping their nanotoxicity properties to a minimum. All the nanoparticle formulations tested herein were found to be biocompatible against non-cancerous and cancer cells by cytotoxicity assays. We also investigated the effect of resulting bare particles, PLL/Ser-SPIONs, on the clonogenicity of cancer cells. According to the results, the cells exhibited colony formation ability depending on the concentration of the nanoparticles and PLL/Ser-SPIONs did not block clonogenicity, except at very high doses. Taken together, our findings imply that these new PLL/Ser-SPIONs can be considered as a safe and promising carrier candidate to be used and developed for further siRNA-based applications. • A new siRNA nanocarrier system composed of SPIONs coated with sericin, and modified with PLL was successfully synthesized.. • High siRNA binding efficiency was achieved by incorporating the siRNA with the PLL/Ser-SPIONs. • siRNA loaded PLL/Ser-SPIONs exhibited sustained in vitro siRNA release kinetics. • Cytotoxicity and colony formation assays revealed that PLL/Ser-SPIONs were biocompatible and safe materials. • Our work suggests that PLL/Ser-SPIONs can be a promising siRNA carrier candidate for gene silencing therapies.

Numerical duality of MHD stagnation point flow and heat transfer of nanofluid past a shrinking/stretching sheet: Metaheuristic approach

In the present era of Industry 4.0, automation, and nanotechnology, many industrial applications require the simultaneous control of heat and fluid flow for better efficiency of machines. The polymeric excursion process, manufacturing of plastic films, glass, metallic equipment, all need control over friction forces and heat flow rates. Considering the importance of the subject, the present study deals with the stagnation point flow and heat transfer of water-based nanofluid over a stretching/shrinking sheet with a non-aligned axis of symmetry. The permeable sheet is considered in the presence of a uniform magnetic field. The non-linear partial differential equations governing the flow and heat transfer are converted into non-linear coupled ordinary differential equations using similarity transformations. The resultant equations are solved using “Particle Swarm Optimization” and Runge-Kutta method based hybrid shooting technique. Considering the nanoparticle size, concentration and shape-dependence on physical and thermal properties of nanofluid more realistic aggregation based mathematical models are used for both viscosity and thermal conductivity. Numerical results for the velocity profile, non-alignment function, temperature distribution and local skin friction are discussed with respect to the physical parameters like nanoparticle concentration, nanoparticle size, magnetic field, suction, and stretching/shrinking velocity. The existence of dual solutions are observed for the shrinking velocity parameter λ<−1, and the practically realizable and stable solutions are filtered out by computing the eigenvalues for the formulated perturbed Eigen problem. The results for the stable solutions unveiled that, by changing the stretching velocity parameter λ from 0 to 0.5, there is approximately 38% enhancement in heat transfer rate and 42% decrement in skin friction coefficient. Moreover, in the case of shrinking velocity parameter λ=−1.25, with an increase in nanoparticle concentration from 0 to 5%, the skin friction coefficient reduces by 53%, whereas the change in nanoparticle size from 10 nm to 50 nm has a skin friction reduction of only 10%.

Precipitation of Pt Nanoparticles inside Ion-Track-Etched Capillaries

Ion-track-etched capillaries containing nanoparticles of precious metals (e.g., Pt, Au, and Ag) can be applied to plasmonic absorber materials. The precipitation of homogeneous and highly dispersed precious metal nanoparticles inside capillaries represents a key process. Ion-track-etched capillaries (diameter: ~500 nm, length: ~25 μm) were created in polyimide film by 350 MeV Xe irradiation (3 × 107 ions/cm2) and chemical etching (using a sodium hypochlorite solution). The films with capillaries were immersed in an aqueous solution containing 0.1–10 mmol/L H2PtCl6 and 0.5 vol% C2H5OH, and then irradiated with a 2 MeV electron beam up to a fluence of 1.4 × 1016 e/cm2. The Pt particles inside the capillaries were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The precipitation of Pt nanoparticles and isolated aggregates inside the capillaries was confirmed by TEM. The Pt nanoparticles tended to aggregate under increasing concentrations of H2PtCl6 in the aqueous solution; meanwhile, no changes in nanoparticle size were noted under increasing electron beam fluence. The results suggest that the proposed method can be used to form metal nanoparticles in nanosized capillaries with a high aspect ratio.

Redox-Responsive Polymeric Nanocomplex for Delivery of Cytotoxic Protein and Chemotherapeutics.

Responsive delivery of anticancer proteins into cells is an emerging field in biological therapeutics. Currently, the delivery of proteins is highly compromised by multiple successive physiological barriers that reduce the therapeutic efficacy. Hence, there is a need to design a robust and sustainable nanocarrier to provide suitable protection of proteins and overcome the physiological barriers for better cellular accumulation. In this work, polyethylenimine (PEI) cross-linked by oxaliplatin(IV) prodrug (oxliPt(IV)) was used to fabricate a redox-responsive nanocomplex (PEI-oxliPt(IV)@RNBC/GOD) for the delivery of a reactive oxygen species-cleavable, reversibly caged RNase A protein (i.e., RNase A nitrophenylboronic conjugate, RNBC) and glucose oxidase (GOD) in order to realize efficient cancer treatment. The generation of hydrogen peroxide by GOD can uncage and restore the enzymatic activity of RNBC. On account of the responsiveness of the nanocomplex to highly reducing cellular environment, it would dissociate and release the protein and active oxaliplatin drug, causing cell death by both catalyzing RNA degradation and inhibiting DNA synthesis. As assessed by the RNA degradation assay, the activity of the encapsulated RNBC was recovered by the catalytic production of hydrogen peroxide from GOD and glucose substrate overexpressed in cancer cells. Monitoring of the changes in nanoparticle size confirmed that the nanocomplex could dissociate in the reducing environment, with the release of active oxaliplatin drug and protein. Confocal laser scanning microscopy (CLSM) and flow cytometry analysis revealed highly efficient accumulation of the nanocomplex as compared to free native proteins. In vitro cytotoxicity experiments using 4T1 cancer cells showed ∼80% cell killing efficacy, with highly efficient apoptosis induction. Assisted by the cationic polymeric carrier, it was evident from CLSM images that intracellular delivery of the therapeutic protein significantly depleted the RNA level. Thus, this work provides a promising platform for the delivery of therapeutic proteins and chemotherapeutic drugs for efficient cancer treatment.

Exploring the enzymatic degradation of poly(glycerol adipate)

Poly(glycerol adipate) (PGA) is a biodegradable, biocompatible, polymer with a great deal of potential in the field of drug delivery. Active drug molecules can be conjugated to the polymer backbone or encapsulated in self-assembled nanoparticles for targeted and systemic delivery. Here, a range of techniques have been used to characterise the enzymatic degradation of PGA extensively for the first time and to provide an indication of the way the polymer will behave and release drug payloads in vivo. Dynamic Light Scattering was used to monitor change in nanoparticle size, indicative of degradation. The release of a fluorescent dye, coupled to PGA, upon incubation with enzymes was measured over a 96 h period as a model of drug release from polymer drug conjugates. The changes to the chemical structure and molecular weight of PGA following enzyme exposure were characterised using FTIR, NMR and GPC. These techniques provided evidence of the biodegradability of PGA, its susceptibility to degradation by a range of enzymes commonly found in the human body and the polymer’s potential as a drug delivery platform.

In-situ HVEM observation under 2 MeV electron irradiations on Y–Ti–O nanoparticles in 12Cr-ODS steel at 723K

The objective of this study is to investigate the microstructural evolution of Y–Ti–O nanoparticles in ferritic 12Cr-ODS steel under in-situ electron radiation. 2 MeV high voltage electron microscope (HVEM) was used for the direct in-situ observation of microstructural evolution at 723 K. The focused beam technique was employed to study the effect of vacancy concentration gradient where the electron beam intensity has a Gaussian distribution. Unlike the typically reported monotonic size change of nanoparticles, under both the focused and uniform beam irradiation, rapid growth and shrinkage were simultaneously observed in each irradiation time step then gradually stabilized. Each nanoparticle did not follow a periodic volumetric change pattern, and this stochastic behavior of Y–Ti–O nanoparticles at the early irradiation stage is first reported in this paper. However, on the contrary to the stochastic volumetric change in each short-time irradiation, from the total volumetric change perspective, the nanoparticles were stable. Thus, the simple total volumetric change of nanoparticles after the irradiation could be inaccurate to fully describe the microstructural evolution of nanoparticles. The shape evolution was observed to investigate the change in morphology and represented by eccentricity and based on different size groups of the nanoparticles, the eccentricity evolution trend was different under the irradiation.

Chemotherapy drug temozolomide adsorbed onto iron-oxide (Fe3O4) nanoparticles as nanocarrier: A simulation study

The adsorption of different temozolomide concentrations onto 1 to 6.9 nm Fe3O4 nanoparticles (to be employed as nanocarriers) is investigated within a molecular dynamics study and Monte Carlo simulated annealing scheme. Bonding modes are investigated with reference to chemisorption, physisorption as well as hydrogen bonding in the context of bond strength (binding energy) as a function of both the temozolomide molecule's loading as well as a change in nanoparticle size from 1 nm up to 6.9 nm. Density functional theory (DFT) simulations are also performed to investigate the conditions for charge transfer from the temozolomide surfactant via the highest occupied molecular orbitals (HOMO), lowest unoccupied molecular orbitals (LUMO) as well as the electrostatic potentials. From this the preferential sites for both electrophilic and nucleophilic attacks were calculated. It is shown that the most reactive sites are the oxygen (O-17 and O-8) as well as nitrogen (N-12) atomic sites which was confirmed by the Monte Carlo molecular dynamics calculations to be reactive with the Fe2+ and Fe3+ ions of the NP surface. Interaction with the O-8 oxygen site was not as prominent as originally anticipated and this was shown by observing the positions of the HOMO and LUMO isosurfaces that were more prominently centred on the O-17 site.

High-pressure dispersion of nanoparticle agglomerates through a continuous aerosol disperser

By discharging aerosols from a high-pressure vessel through a nozzle, an improved continuous aerosol dispersion system can disperse nanoparticle agglomerates to almost primary nanoparticle size. The system’s high-pressure dispersion was modelled and numerically simulated using the Taylor expansion method of moments. The strong turbulent shear near the nozzle could achieve the same level as the van der Waals force, which is the main mechanism for deagglomerating nanoparticle agglomerates. The change in nanoparticle size was determined to be proportional to the pressure drop between the nozzle inlet and outlet. Nanoparticle breakup was also observed to be affected by the fractional dimension and primary size of particles.

Smaller CpG-Conjugated Gold Nanoconstructs Achieve Higher Targeting Specificity of Immune Activation

This study describes a side-by-side comparison of the in vitro immunostimulatory activity of cytosine-phosphate-guanine (CpG)-conjugated gold nanoparticles. Three different gold nanoparticle cores (13 nm spheres, 50 nm spheres, and 40 nm stars) with the same CpG surface density were investigated for toll-like receptor 9 activation. For this parameter set, 13 nm spheres displayed significantly higher specificity for targeting immune receptors and larger nanoparticles (50 nm spheres and 40 nm stars) showed higher cellular uptake and higher immune activation because of off-target effects. Changes in nanoparticle size and presentation of activating ligands affect construct-induced immune responses at different levels, and care must be taken when considering practical and global design rules for CpG delivery.

Design of Histone-Mimic Nanoparticles for DNA and RNA Compaction using Molecular Modeling

The design of nanoparticles that can induce specific structural transitions in nucleic acids is important for nanotechnology applications including gene delivery and nanoelectronics. It is known that in biological systems, the binding of cationic proteins induces structural changes in DNA or RNA, which can affect gene expression or cause the compaction of DNA into chromatin. The anionic backbone of the nucleic acids DNA and RNA allow for non-specific electrostatic interactions with cationic proteins, nanoparticles, or dendrimers. The interaction of nucleic acids and nanoparticles may be tuned through changes in nanoparticle size, charge, polarity, or shape. However, the factors that affect structural transitions are not fully understood. We performed atomistic molecular dynamics simulations of the binding of nucleic acids to monolayer-protected gold nanoparticles to elucidate structural changes that take place for nanoparticles and DNA upon binding. Results from these simulations were analyzed to determine modes of DNA and RNA bending with nanoparticles. Our simulations show that highly charged nanoparticles cause DNA to bend with little damage to the helix structure, similar to DNA in the nucleosome. Nanoparticle shape as well as charge is shown to affect the wrapping of nucleic acids with the nanoparticle. Low salt concentrations and high nanoparticle charge cause greater disruptions to DNA structure. We find that the roll parameter is the most important base-pair parameter for DNA bending. Requirements for bending differed significantly between DNA and dsRNA. The degree of DNA bending is controlled by the charge of the NPs, but ligand flexibility played a more significant role in dsRNA bending. We have shown that functionalized gold NPs can be designed to wrap and compact both RNA an DNAs with fine control of binding strength through NP charge and ligand chemistry.

Gold nanoparticle colorants as traditional ceramic glaze alternatives

AbstractHistorically, Roman stained glass has been a standard for high‐temperature color stability since biblical times but was not properly characterized as emission from nanoparticle plasmon resonance until the 1990s. The methods under which it was created have been lost, but some efforts have recently been made to recreate these properties using gold nanoparticle inks on glassy surfaces. This body of work employs gold nanoparticle systems ranging from 0.015% to 0.100% (wt/wt), suspended in a clear glaze body. The glazes are fired with traditional ceramic methods—in both gas reduction and electric oxidation kilns—in which nanoparticles are retained and can be imaged via TEM. Various colors intensities are reported in addition to changes in nanoparticle size after application and firing. The nanoparticle glazes are compared to traditional red glazes, highlighting the significantly lower metal loading required (5%‐10% for traditional glazes vs 0.100% for gold (wt/wt)), therein. Finally, proof of concept is provided with a functional gold nanoparticle mug, fired in reduction, that costs roughly 0.98$ USD in gold used.

Reversibly Manipulating the Surface Chemistry of Polymeric Nanostructures via a "Grafting To" Approach Mediated by Nucleobase Interactions.

“Grafting to” polymeric nanostructures or surfaces is a simple and versatile approach to achieve functionalization. Herein, we describe the formation of mixed polymer-grafted nanoparticles through a supramolecular “grafting to” method that exploits multiple hydrogen-bonding interactions between the thymine (T)-containing cores of preformed micelles and the complementary nucleobase adenine (A) of added diblock copolymers. To demonstrate this new “grafting to” approach, mixed-corona polymeric nanoparticles with different sizes were prepared by the addition of a series of complementary diblock copolymers containing thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) to a preformed micelle with a different coronal forming block, poly(4-acryloylmorpholine) (PNAM). PNIPAM chains were distributed throughout the corona and facilitated a fast and fully reversible size change of the resulting mixed-corona micelles upon heating. Through the introduction of an environmentally sensitive fluorophore, the reversible changes in nanoparticle size and coronal composition could be easily probed. Furthermore, preparation of mixed-corona micelles also enabled ligands, such as d-mannose, to be concealed and displayed on the micelle surface. This supramolecular “grafting to” approach provides a straightforward route to fabricate highly functionalized mixed polymeric nanostructures or surfaces with potential applications in targeted diagnosis or therapy and responsive surfaces.

Rapid Kinetics of Size and pH-Dependent Dissolution and Aggregation of Silver Nanoparticles in Simulated Gastric Fluid.

As silver nanoparticles (AgNPs) are used in a wide array of commercial products and can enter the human body through oral exposure, it is important to understand the fundamental physical and chemical processes leading to changes in nanoparticle size under the conditions of the gastrointestinal (GI) tract. Rapid AgNP growth was observed using nanoparticle tracking analysis with 30 s resolution over a period of 17 min in simulated gastric fluid (SGF) to explore rapid kinetics as a function of pH (SGF at pH 2, 3.5, 4.5 and 5), size (20 and 110 nm AgNPs), and nanoparticle coating (citrate and PVP). Growth was observed for 20 nm AgNP at each pH, decreasing in rate with increasing pH, with the kinetics shifting from second-order to first-order. The 110 nm AgNP showed growth at ≤3.5 pH, with no growth observed at higher pH. This behavior can be explained by the generation of Ag+ in acidic environments, which precipitates with Cl-, leading to particle growth and facilitating particle aggregation by decreasing their electrostatic repulsion in solution. These results highlight the need to further understand the importance of initial size, physicochemical properties, and kinetics of AgNPs after ingestion to assess potential toxicity.

Nanoparticle‐Bound Cytolytic Peptide Prodrugs for Cancer Therapy

ObjectiveTo develop a nanoparticle platform which promotes the delivery of cytolytic peptide prodrugs to tumors and their activation by locally produced proteases.Introduction: Melittin is a peptide toxin derived from bee venom which has been proposed as a cancer therapy due to its cytolytic activity. Yet, its therapeutic applications have been limited by its nonspecific cytotoxicity and rapid clearance from the circulation. We have previously developed a prodrug form of melittin which is activated upon cleavage by matrix metalloproteinase 9 (MMP‐9), a protease closely linked with tumor growth and metastasis. Here, we present a platform for delivery of this prodrug based on a perfluorocarbon nanoparticle system designed to enhance intratumoral accumulation while permitting prodrug activation by local MMP‐9 activity.Methods and Results: Incubation of the melittin prodrug with perfluorocarbon nanoparticles (NPs) resulted in stable loading of 10,250 peptides per NP with no significant change in NP size. Addition of 20 nM MMP‐9 led to activation of 57.8% of NP‐bound prodrug within 3 hours. B16F10 melanoma cell viability was virtually eliminated following incubation with 50 μM free or NP‐bound prodrug in the presence of MMP‐9 (p &lt; 0.001 compared to control). In a mouse model of B16F10 lung metastasis, NP accumulation in lung tumors was demonstrated by both fluorescence microscopy (Figure A; NPs in red) and quantitative 19F magnetic resonance spectroscopy (Figure B). Gelatin zymography confirmed production of active MMP‐9 by these tumors.ConclusionPerfluorocarbon nanoparticles accumulate within tumors and permit activation of bound prodrugs, making them promising delivery vehicles for cytolytic peptide agents.Research Support: NIH R01 HL073646 image image

Modeling coupled nanoparticle aggregation and transport in porous media: A Lagrangian approach

Changes in nanoparticle size and shape due to particle–particle interactions (i.e., aggregation or agglomeration) may significantly alter particle mobility and retention in porous media. To date, however, few modeling studies have considered the coupling of transport and particle aggregation processes. The majority of particle transport models employ an Eulerian modeling framework and are, consequently, limited in the types of collisions and aggregate sizes that can be considered. In this work, a more general Lagrangian modeling framework is developed and implemented to explore coupled nanoparticle aggregation and transport processes. The model was verified through comparison of model simulations to published results of an experimental and Eulerian modeling study (Raychoudhury et al., 2012) of carboxymethyl cellulose (CMC)-modified nano-sized zero-valent iron particle (nZVI) transport and retention in water-saturated sand columns. A model sensitivity analysis reveals the influence of influent particle concentration (ca. 70 to 700mg/L), primary particle size (10–100nm) and pore water velocity (ca. 1–6m/day) on particle–particle, and, consequently, particle–collector interactions. Model simulations demonstrate that, when environmental conditions promote particle–particle interactions, neglecting aggregation effects can lead to under- or over-estimation of nanoparticle mobility. Results also suggest that the extent to which higher order particle–particle collisions influence aggregation kinetics will increase with the fraction of primary particles. This work demonstrates the potential importance of time-dependent aggregation processes on nanoparticle mobility and provides a numerical model capable of capturing/describing these interactions in water-saturated porous media.