Understanding Of Nano-bio Interactions Research Articles

Effect of ligand and shell densities on the surface structure of core-shell nanoparticles self-assembled from function-spacer-lipid constructs.

Biomolecular corona is the major obstacle to the clinical translation of nanomedicines. Since corona formation is governed by molecular interactions at the nano-bio interface, nanoparticle surface properties such as topography, charge and surface chemistry can be tuned to manipulate biomolecular corona formation. To this end, as the first step towards a deep understanding of the processes of corona formation, it is necessary to develop nanoparticles employing various biocompatible materials and characterize their surface structure and dynamics at the molecular level. In this work, we applied molecular dynamics simulation to study the surface structure of organic core-shell nanoparticles formed by the self-assembly of synthetic molecules composed of a DOPE lipid, a carboxymethylglycine spacer and biotin. Lipid moieties form the hydrophobic core, spacer motifs serve as a hydrophilic shell and biotin residues function as a targeting ligand. By mixing such function-spacer-lipid, spacer-lipid and lipid-only constructs at various molar ratios, densities of the ligand and spacer on the nanoparticle surface were modified. For convenient analysis of the structure and dynamics of all regions of the nanoparticle surface, we compiled topography maps based on atomic coordinates. It was shown that an increase in the density of the shell does not reduce exposure of the core, but increases shell average thickness. Biotin, due to its alkyl valeric acid chain and spacer flexibility, is localized primarily near the hydrophobic core and its partial presentation on the surface occurs only in nanoparticles with higher ligand densities. However, an increase in biotin density leads to its clustering. In turn, ligand clustering diminishes the stealth properties of the shell and targeting efficiency. Based on nanoparticle surface structures, we determined the optimal density of biotin. Experimental studies reported in the literature confirm these conclusions. We also suggest design tips to achieve the preferred biotin presentation. Simulation results are consistent with the synchrotron SAXS profile. We believe that such studies will contribute to a better understanding of nano-bio interactions towards the rational design of efficient drug delivery systems.

Influence of Administration Route and Dose on Biodistribution Profile and Effects of PEG-PLA Nanoparticles in Mice

Polyethylene glycol-polylactic acid nanoparticles (PEG-PLA NPs) represent a new generation of parenteral therapeutics systems. Following administration, these NPs possess the potential to interact with biological machinery. Therefore, it is essential to get a systematic understanding of the biological fate of these NPs to evaluate their safety. In the present study, two doses (20 and 40 mg/kg) of technetium-99m labeled PEG-PLA NPs were administered intravenous (i.v.) and oral into mice and the distribution was assessed at 1, 2, 4 and 24 h post administration. Biodistribution and blood kinetic profiles revealed the extended systemic circulation of the NPs. Dose-dependent presence of NPs (p<0.05) was detected in the blood, liver, lung, spleen, and kidney of i.v. injected mice, and also in the blood, lung, spleen, stomach, and intestine of oral administered mice. The consequences of NP interaction with the biological components were studied by measurement of hematology, oxidative stress, genotoxic and histological parameters. Significantly increased levels of oxidative stress markers such as glutathione were observed in the liver, and spleen of i.v. injected mice and liver, stomach, and intestine of orally treated mice. Decreased lipid peroxidation levels (p<0.05) were observed in the liver of orally treated mice versus untreated mice. Even though PEG-PLA NPs have been shown to induce oxidative DNA damage, interestingly no histological lesions were observed in selected organs except lung of i.v. treated mice, which showed moderate vascular congestion. Such insights on in vivo distribution and understanding of nano-bio interactions at molecular and genetic levels are considered fundamental for the designing of safer nanoparticles for biomedical applications.

High-Resolution Single Particle Zeta Potential Characterisation of Biological Nanoparticles using Tunable Resistive Pulse Sensing

Physicochemical properties of nanoparticles, such as size, shape, surface charge, density, and porosity play a central role in biological interactions and hence accurate determination of these characteristics is of utmost importance. Here we propose tunable resistive pulse sensing for simultaneous size and surface charge measurements on a particle-by-particle basis, enabling the analysis of a wide spectrum of nanoparticles and their mixtures. Existing methodologies for measuring zeta potential of nanoparticles using resistive pulse sensing are significantly improved by including convection into the theoretical model. The efficacy of this methodology is demonstrated for a range of biological case studies, including measurements of mixed anionic, cationic liposomes, extracellular vesicles in plasma, and in situ time study of DNA immobilisation on the surface of magnetic nanoparticles. The high-resolution single particle size and zeta potential characterisation will provide a better understanding of nano-bio interactions, positively impacting nanomedicine development and their regulatory approval.

Biological and environmental surface interactions of nanomaterials: characterization, modeling, and prediction.

The understanding of nano-bio interactions is deemed essential in the design, application, and safe handling of nanomaterials. Proper characterization of the intrinsic physicochemical properties, including their size, surface charge, shape, and functionalization, is needed to consider the fate or impact of nanomaterials in biological and environmental systems. The characterizations of their interactions with surrounding chemical species are often hindered by the complexity of biological or environmental systems, and the drastically different surface physicochemical properties among a large population of nanomaterials. The complexity of these interactions is also due to the diverse ligands of different chemical properties present in most biomacromolecules, and multiple conformations they can assume at different conditions to minimize their conformational free energy. Often these interactions are collectively determined by multiple physical or chemical forces, including electrostatic forces, hydrogen bonding, and hydrophobic forces, and calls for multidimensional characterization strategies, both experimentally and computationally. Through these characterizations, the understanding of the roles surface physicochemical properties of nanomaterials and their surface interactions with biomacromolecules can play in their applications in biomedical and environmental fields can be obtained. To quantitatively decipher these physicochemical surface interactions, computational methods, including physical, statistical, and pharmacokinetic models, can be used for either analyses of large amounts of experimental characterization data, or theoretical prediction of the interactions, and consequent biological behavior in the body after administration. These computational methods include molecular dynamics simulation, structure-activity relationship models such as biological surface adsorption index, and physiologically-based pharmacokinetic models. WIREs Nanomed Nanobiotechnol 2017, 9:e1440. doi: 10.1002/wnan.1440 For further resources related to this article, please visit the WIREs website.