What to measure? is a key question in nanoscience, and it is not straightforward to address as different physicochemical properties define a nanoparticle sample. Most prominent among these properties ...are size, shape, surface charge, and porosity. Today researchers have an unprecedented variety of measurement techniques at their disposal to assign precise numerical values to those parameters. However, methods based on different physical principles probe different aspects, not only of the particles themselves, but also of their preparation history and their environment at the time of measurement. Understanding these connections can be of great value for interpreting characterization results and ultimately controlling the nanoparticle structure–function relationship. Here, the current techniques that enable the precise measurement of these fundamental nanoparticle properties are presented and their practical advantages and disadvantages are discussed. Some recommendations of how the physicochemical parameters of nanoparticles should be investigated and how to fully characterize these properties in different environments according to the intended nanoparticle use are proposed. The intention is to improve comparability of nanoparticle properties and performance to ensure the successful transfer of scientific knowledge to industrial real‐world applications.
Nanoparticles exist in various chemical compositions; however, their behavior is largely governed by their nanometer dimensions. Characterization of their physicochemical parameters is therefore fundamental for understating their structure–function relationship. An overview of the major methods and some recommendations for the precise measurements of these fundamental properties are offered.
Since their discovery, carbon dots (CDs) have been a promising nanomaterial in a variety of fields including nanomedicine. Despite their potential in this area, there are many obstacles to overcome ...for CDs to be approved for biomedical use. One major hindrance to CDs’ approval is related to their poorly defined structure. Herein a structural study of CDs is presented in order to rectify this shortcoming. The properties of three CDs which have significant promise in biomedical applications, black CDs (B-CDs), carbon nitride dots (CNDs), and yellow CDs (Y-CDs), are compared in order to develop a coherent structural model for each nanosystem. Absorption coefficients were measured for each system and this data gave insight on the level of disorder in each system. Furthermore, extensive structural characterization has been performed in order to derive structural information for each system. This data showed that B-CDs and CNDs are functionalized to a greater degree and are also more disordered and amorphous than Y-CDs. These techniques were used to develop a structural model consistent with the obtained data and what is known for carbonic nanostructures. These models can be used to analyze CD emission properties and to better understand the structure-property relationship in CDs.
This graphic illustrates the stark distinction in properties between certain carbon dots (CDs). This work highlights the large diversity of properties among CDs and endeavors to go beyond the spherical shape typically associated with this material to see the core structure and understand the formation of CDs. Display omitted
The nanomaterial industry generates gigantic quantities of metal-based nanomaterials for various technological and biomedical applications; however, concomitantly, it places a massive burden on the ...environment by utilizing toxic chemicals for the production process and leaving hazardous waste materials behind. Moreover, the employed, often unpleasant chemicals can affect the biocompatibility of the generated particles and severely restrict their application possibilities. On these grounds, green synthetic approaches have emerged, offering eco-friendly, sustainable, nature-derived alternative production methods, thus attenuating the ecological footprint of the nanomaterial industry. In the last decade, a plethora of biological materials has been tested to probe their suitability for nanomaterial synthesis. Although most of these approaches were successful, a large body of evidence indicates that the green material or entity used for the production would substantially define the physical and chemical properties and as a consequence, the biological activities of the obtained nanomaterials. The present review provides a comprehensive collection of the most recent green methodologies, surveys the major nanoparticle characterization techniques and screens the effects triggered by the obtained nanomaterials in various living systems to give an impression on the biomedical potential of green synthesized silver and gold nanoparticles.
Using fluorescence microscopy, it is shown that most RNA-loaded lipid nanoparticles in the ensemble contain nucleic acid cargo. The same is true for lipid nanoparticles containing siRNA or pDNA.
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Nucleic acid-based therapies are transforming medicine, but rely on an efficient delivery vehicle such as lipid nanoparticles (LNPs). Concerns exists in the nanomedicine field, that a large fraction of the LNPs in the ensemble does not contain any nucleic acid cargo and thus exert no functional effect. Nevertheless, how LNP lipid formulation, the LNP preparation method employed and nucleic acid cargo size correlates with the proportion of empty LNPs remains largely unexplored. Here we employ a well-established single particle based method to study nucleic acid loading heterogeneity in LNPs. We find that only a minor fraction of LNPs are “empty”, both for LNPs loaded with siRNA, mRNA and plasmids. For clinically relevant LNPs for mRNA delivery, we never detected more than 16% empty nanoparticles in the ensemble. Thus employing standard LNP lipid-cargo combinations and preparation schemes results in LNPs with the potential to serve their biomedical function.
As a consequence of their increase in annual production and widespread distribution in the environment, nanoparticles potentially pose a significant public health risk. The sought-after catalytic ...activity granted by their physiochemical properties doubles as a hazard to physiological processes following exposure through inhalation, oral, transdermal, subcutaneous, and intravenous uptake. Upon uptake into the body, their size, morphology, surface charge, coating, and chemical composition augment the response of biological systems to the materials and enhance their toxicity. Identification of each property is necessary to predict the harm imposed by foreign nanomaterials in the body. Assay methods ranging from endotoxin and lactate dehydrogenase (LDH) signaling to apoptosis and oxidative stress detection supply valuable techniques for exposing biomarkers of nanoparticle-induced cellular damage. Spectroscopic investigation of epithelial barrier permeation and distribution within living cells reveals the proclivity of nanoparticles to penetrate the body's natural defensive boundaries and deposit themselves in cytotoxic locations. Combination of the various characterization methodologies and assays is required for every new nanoparticulate system despite preexisting data for similar systems due to the lack of deterministic trends among investigated nanoparticles. The propensity of nanomaterials to denature proteins and oxidize substrates in their local environment generates significant concern for the applicability of several traditional in vitro assays, and the modification of susceptible approaches into novel methods suitable for the evaluation of nanoparticles comprises the focus of future work centered on nanoparticle toxicity analysis.
Ultrasensitive detection and characterization of single nanoparticles (<100 nm) is important in nanotechnology and life sciences. Direct measurement of the elastically scattered light from individual ...nanoparticles represents the simplest and the most direct method for particle detection. However, the sixth-power dependence of scattering intensity on particle size renders very small particles indistinguishable from the background. Adopting strategies for single-molecule fluorescence detection in a sheathed flow, here we report the development of high sensitivity flow cytometry (HSFCM) that achieves real-time light-scattering detection of single silica and gold nanoparticles as small as 24 and 7 nm in diameter, respectively. This unprecedented sensitivity enables high-resolution sizing of single nanoparticles directly based on their scattered intensity. With a resolution comparable to that of TEM and the ease and speed of flow cytometric analysis, HSFCM is particularly suitable for nanoparticle size distribution analysis of polydisperse/heterogeneous/mixed samples. Through concurrent fluorescence detection, simultaneous insights into the size and payload variations of engineered nanoparticles are demonstrated with two forms of clinical nanomedicine. By offering quantitative multiparameter analysis of single nanoparticles in liquid suspensions at a throughput of up to 10 000 particles per minute, HSFCM represents a major advance both in light-scattering detection technology and in nanoparticle characterization.
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•ElFFF provides information on hydrodynamic diameter of nanoparticles.•SP-ICP-MS provides information on core diameter of nanoparticles.•ElFFF with SP-ICP-MS provides information on ...electrophoretic mobility of nanoparticles.•ElFFF with SP-ICP-MS provides information on stabilizer layer thickness on nanoparticle surface.
Electrical field-flow fractionation (ElFFF) is a sub-technique of field-flow fractionation utilized for separation of charged nanoparticles. ElFFF was applied for characterization of size and charge of nanoparticles by investigating the nanoparticle retention time. However, one of the parameters; i.e., size or charge of nanoparticles, must be known before characterizing another parameter. This work illustrates an application of normal ElFFF for nanoparticle characterization associated with single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) which was used for size determination. Six nanoparticles samples including 30 nm AuNPs stabilized by citrate, 60 nm AuNPs stabilized by citrate, mixture of 30 nm and 60 nm AuNPs stabilized by citrate, 60 nm silver nanoparticles (AgNPs) stabilized by polyethylene glycol (PEG), 100 nm AgNPs stabilized by citrate, and mixture of 60 nm AgNPs stabilized by PEG and 100 nm AgNPs stabilized by citrate were used as samples. The nanoparticles were prior separated in ElFFF system under 1.50 V applied voltage in deionized (DI) water carrier, then their fractions were collected for size determination using SP-ICP-MS. The charge, electrophoretic mobility, of nanoparticles was characterized by using the size determined from SP-ICP-MS and the retention time of nanoparticles via the ElFFF theoretical equation. The size and charge of nanoparticles characterized using ElFFF and SP-ICP-MS were in agreement with their size and charge reported in certificate. In addition, the size information obtained from ElFFF and SP-ICP-MS was applied for characterization of the layer thickness of stabilizing agent coated on nanoparticle surface of 60 nm AgNPs stabilized by PEG. With high sensitivity of inductively coupled plasma mass spectrometry (ICP-MS), this method shows potential use for characterization of nanoparticles in environmental system.
•Particle size distribution and concentration of PS-DI colloids are measured via LES.•Sensitivity of LES to refractive index uncertainties & system noise is investigated.•Experimentally characterized ...noise profile is embedded into numerical simulations.•Wavelength spectrum limited to high SNR region improves the LES results.•In-situ calibration of complex refractive index enhances the quality of LES results.•Both mono and bi-modal size distributions are experimentally retrieved.
The measurement of particle size distribution (PSD) in colloids and nanofluids presents many challenges, especially when it requires to be conducted in-situ and real-time. Our work aims to assess the capabilities of Light Extinction Spectroscopy (LES) technique to determine concentration and volumetric PSD (vPSD) of colloids and nanofluids. Numerical simulations are performed to verify robustness of LES data inversion algorithm and to identify the most relevant uncertainty sources. Experiments are carried out on well-dispersed water based colloids containing Polystyrene particles with median diameters at 120 nm and 300 nm. LES results are compared with supplier’s data, 3D-DLS measurements, and SEM images. Via sensitivity analyses, LES sensitivity to particle complex refractive index spectrum and to system noise level are examined. To improve accuracy, we limit LES data inversion at shorter wavelengths where high SNR is acquired. The noise is experimentally characterized and embedded into numerical simulations to better mimic the real conditions. We show that while noise level affects mostly vPSDs’ peak height, small inaccuracies in complex refractive index spectrum deteriorate the stability of the inversion, especially for smaller vPSDs. To overcome the latter, we carry out a preliminary in-situ calibration on particle complex refractive index spectrum. Accordingly, results are substantially improved with maximal discrepancies smaller than 3% for median and volume mean diameters, and lower than 13% for number concentrations. Besides, the retrieval of bi-modal distribution is promising. In conclusion, our methodology can be considered as a guideline to evaluate the applicability and accuracy of the LES technique in colloids.
Titanium dioxide nanoparticles (TiO2 NPs) are among the most commonly used nanomaterials and are most likely to end up in soil. Therefore, it is pertinent to study the interaction of TiO2 NPs with ...soil microorganisms. The present in vitro broth study evaluates the impacts of low‐dose treatments (0, 1.0, 5.0, 10.0, 20.0, and 40.0 mg L−1) of TiO2 NPs on cell viability, morphology, and plant growth promoting (PGP) traits of rhizobia isolated from mung bean root nodule. Two types of TiO2 NPs, that is, mixture of anatase and rutile, and anatase alone were used in the study. These TiO2 NPs were supplemented in broth along with a multifunctional isolate (Bradyrhizobium sp.) and two reference cultures. The exposure of TiO2 (anatase+rutile) NPs at low concentrations (less than 20.0 mg L−1) enhanced the cell growth, and total soluble protein content, besides improving the phosphate solubilization, Indole‐3‐acetic acid (IAA) production, siderophore, and gibberellic acid production. The TiO2 (anatase) NPs enhanced exopolysaccharide (EPS) production by the test rhizobial cultures. The radical scavenging assay was performed to reveal the mode of action of the nano‐TiO2 particles. The study revealed higher reactive oxygen species (ROS) generation by the TiO2 (anatase) NPs as compared with TiO2 (anatase+rutile) NPs. Exposure to TiO2 NPs also altered the morphology of rhizobial cells. The findings suggest that TiO2 NPs could act as promoters of PGP traits of PGP bacteria when applied at appropriate lower doses.
Solid-lipid nanoparticles and nanostructured lipid carriers are delivery systems for the delivery of drugs and other bioactives used in diagnosis, therapy, and treatment procedures. These ...nanocarriers may enhance the solubility and permeability of drugs, increase their bioavailability, and extend the residence time in the body, combining low toxicity with a targeted delivery. Nanostructured lipid carriers are the second generation of lipid nanoparticles differing from solid lipid nanoparticles in their composition matrix. The use of a liquid lipid together with a solid lipid in nanostructured lipid carrier allows it to load a higher amount of drug, enhance drug release properties, and increase its stability. Therefore, a direct comparison between solid lipid nanoparticles and nanostructured lipid carriers is needed. This review aims to describe solid lipid nanoparticles and nanostructured lipid carriers as drug delivery systems, comparing both, while systematically elucidating their production methodologies, physicochemical characterization, and in vitro and in vivo performance. In addition, the toxicity concerns of these systems are focused on.
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