The development of highly dense highly protected surfactant ionizable lipid RNA loaded nanoparticles

The long quest for efficient drug administration has been looking for a universal carrier that can precisely transport traditional drugs, new genomic and proteic therapeutic agents. Today, researchers have found conditions to overcome the two main drug delivery dilemmas. On the one side, the versatility of the vehicle to efficiently load, protect and transport the drug and then release it at the target place. On the other hand, the questions related to the degree of PEGylation which are needed to avoid nanoparticle (NP) aggregation and opsonization while preventing cellular uptake. The development of different kinds of lipidic drug delivery vehicles and particles has resulted in the development of ionizable lipid nanoparticles (iLNPs), which can overcome most of the typical drug delivery problems. Proof of their success is the late approval and massive administration as the prophylactic vaccine for SARS-CoV-2. These ILNPs are built by electrostatic aggregation of surfactants, the therapeutic agent, and lipids that self-segregate from an aqueous solution, forming nanoparticles stabilized with lipid polymers, such as PEG. These vehicles overcome previous limitations such as low loading and high toxicity, likely thanks to low charge at the working pH and reduced size, and their entry into the cells via endocytosis rather than membrane perforation or fusion, always associated with higher toxicity. We herein revise their primary features, synthetic methods to prepare and characterize them, pharmacokinetic (administration, distribution, metabolization and excretion) aspects, and biodistribution and fate. Owing to their advantages, iLNPs are potential drug delivery systems to improve the management of various diseases and widely available for clinical use

How Does Immunomodulatory Nanoceria Work? ROS and Immunometabolism

Immunemetabolism; Metabolism; NanoceriaInmunometabolismo; Metabolismo; NanoceriaImmunemetabolisme; Metabolisme; NanocèriaDysregulation of the immune system is associated with an overproduction of metabolic reactive oxygen species (ROS) and consequent oxidative stress. By buffering excess ROS, cerium oxide (CeO2) nanoparticles (NPs) (nanoceria) not only protect from oxidative stress consequence of inflammation but also modulate the immune response towards inflammation resolution. Immunomodulation is the modulation (regulatory adjustment) of the immune system. It has natural and human-induced forms, and it is part of immunotherapy, in which immune responses are induced, amplified, attenuated, or prevented according to therapeutic goals. For decades, it has been observed that immune cells transform from relative metabolic quiescence to a highly active metabolic state during activation(1). These changes in metabolism affect fate and function over a broad range of timescales and cell types, always correlated to metabolic changes closely associated with mitochondria number and morphology. The question is how to control the immunochemical potential, thereby regulating the immune response, by administering cellular power supply. In this regard, immune cells show different general catabolic modes relative to their activation status, linked to their specific functions (maintenance, scavenging, defense, resolution, and repair) that can be correlated to different ROS requirements and production. Properly formulated, nanoceria is highly soluble, safe, and potentially biodegradable, and it may overcome current antioxidant substances limitations and thus open a new era for human health management

Magnetic Domains and Surface Effects in Hollow Maghemite Nanoparticles

In the present work, we investigate the magnetic properties of ferrimagnetic and noninteracting maghemite (g-Fe2O3) hollow nanoparticles obtained by the Kirkendall effect. From the experimental characterization of their magnetic behavior, we find that polycrystalline hollow maghemite nanoparticles are characterized by low superparamagnetic-to-ferromagnetic transition temperatures, small magnetic moments, significant coercivities and irreversibility fields, and no magnetic saturation on external magnetic fields up to 5 T. These results are interpreted in terms of the microstructural parameters characterizing the maghemite shells by means of an atomistic Monte Carlo simulation of an individual spherical shell model. The model comprises strongly interacting crystallographic domains arranged in a spherical shell with random orientations and anisotropy axis. The Monte Carlo simulation allows discernment between the influence of the structure polycrystalline and its hollow geometry, while revealing the magnetic domain arrangement in the different temperature regimes.Comment: 26 pages, 8 figures. In press in Phys. Rev.

Impact of engineered nanoparticles in initiating or modulating pathology-related Inflammation

The possibility that nanomaterials could perturb the normal course of an inflammatory response is a key issue when assessing nano-immunosafety. The alteration of the normal progress of an inflammatory response may have pathological consequences, since inflammation is a major defensive mechanism and its efficiency maintains the body’s health. We can thus consider as pathology-related inflammation those inflammatory reactions that, instead of eliminating foreign agents, lack down-regulation and cause tissue damage. To assess the ability of nanoparticles to initiate and modulate inflammatory reactions, an in vitro model was used that recapitulates all the stages of infection-induced inflammation, from initiation to resolution, based on human primary blood monoytes. A parallel model reproducing pathological chronic inflammation shows that the differences between resolving and persistent inflammation are subtle and evident only upon kinetic analysis of gene expression profiles and production of inflammatory factors. Rigorously endotoxin-free Au and Ag nanoparticles have been assessed for their ability to directly initiate in vitro inflammation and for their capacity to modulate the course both physiological resolving inflammation and pathological persistent inflammation. In no case significant effects were observed, with the exception of a transient increase of the inflammatory response in the presence of Ag nanoparticles. An important issue in the regulation of monocyte/macrophage inflammatory functions is the capacity of innate “memory”, i.e., the ability of respond differently to a challenge if previously primed with the same or a different agent. How nanoparticles can impact innate memory was assessed by using Au nanoparticles as priming and challenge agent with and without LPS and zymosan. Priming with LPS and zymosan could drastically decrease the response of monocytes (production of TNFa) to a challenge with any stimulus, given 7 days after the first. The presence of Au nanoparticles did not influence such behaviour. Likewise, Au nanoparticles did not directly induce memory, i.e., did not influence the response of monocytes to subsequent stimuli. We conclude that Au and Ag nanoparticles, at the size and concentrations used, are taken up by monocytes without this causing any notable interference with their capacity to mount an adequate defensive responses to microbial challenges, either immediate or after some time from exposure. This work was supported by per EU FP7 projects HUMUNITY and BioCog, the H2020 project PANDORA, the CNR Flagship Project InterOmics, and the cluster project Medintech of the Italian Ministry of Education, University and Research

The development of highly dense highly protected surfactant ionizable lipid RNA loaded nanoparticles

Nanopartículas lipídicas ionizables; FarmacocinéticaIonizable lipid nanoparticles; PharmacokineticsNanopartícules lipídiques ionitzables; FarmacocinèticaThe long quest for efficient drug administration has been looking for a universal carrier that can precisely transport traditional drugs, new genomic and proteic therapeutic agents. Today, researchers have found conditions to overcome the two main drug delivery dilemmas. On the one side, the versatility of the vehicle to efficiently load, protect and transport the drug and then release it at the target place. On the other hand, the questions related to the degree of PEGylation which are needed to avoid nanoparticle (NP) aggregation and opsonization while preventing cellular uptake. The development of different kinds of lipidic drug delivery vehicles and particles has resulted in the development of ionizable lipid nanoparticles (iLNPs), which can overcome most of the typical drug delivery problems. Proof of their success is the late approval and massive administration as the prophylactic vaccine for SARS-CoV-2. These ILNPs are built by electrostatic aggregation of surfactants, the therapeutic agent, and lipids that self-segregate from an aqueous solution, forming nanoparticles stabilized with lipid polymers, such as PEG. These vehicles overcome previous limitations such as low loading and high toxicity, likely thanks to low charge at the working pH and reduced size, and their entry into the cells via endocytosis rather than membrane perforation or fusion, always associated with higher toxicity. We herein revise their primary features, synthetic methods to prepare and characterize them, pharmacokinetic (administration, distribution, metabolization and excretion) aspects, and biodistribution and fate. Owing to their advantages, iLNPs are potential drug delivery systems to improve the management of various diseases and widely available for clinical use.We acknowledge financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER,UE) proyectos de I+D+i de programación conjunta internacional MCIN/AEI (CONCORD, PCI2019-103436) cofunded by the European Union and Generalitat de Catalunya (2017-SGR-1431). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya

Nucleation and growth of gold nanoparticles in the presence of different surfactants: a dissipative particle dynamics study

Colloids; Computational chemistry; NanoparticlesColoides; Química computacional; NanopartículasCol·loides; Química computacional; NanopartículesNanoparticles (NPs) show promising applications in biomedicine, catalysis, and energy harvesting. This applicability relies on controlling the material’s features at the nanometer scale. Surfactants, a unique class of surface-active molecules, have a remarkable ability to tune NPs activity; provide specific functions, avoid their aggregation, and create stable colloidal solutions. Surfactants also control nanoparticles’ nucleation and growth processes by modifying nuclei solubility and surface energy. While nucleation seems independent from the surfactant, NP’s growth depends on it. NP`s size is influenced by the type of functional group (C, O, S or N), length of its C chain and NP to surfactant ratio. In this paper, gold nanoparticles (Au NPs) are taken as model systems to study how nucleation and growth processes are affected by the choice of surfactants by Dissipative Particle Dynamics (DPD) simulations. DPD has been mainly used for studying biochemical structures, like lipid bilayer models. However, the study of solid NPs, and their conjugates, needs the introduction of a new metallic component. To represent the collective phenomena of these large systems, their degrees of freedom are reduced by Coarse-Grained (CG) models. DPD behaved as a powerful tool for studying complex systems and shedding some light on some experimental observations, otherwise difficult to explain.Authors are gratefully acknowledged for a fellowship to R.S-L provided by Universitat Autònoma de Barcelona, and for the financial support obtained through grant number RTI2018-099965-B-I00 from Ministerio de Ciencia, Innovación y Universidades, Spain. NGB and VP acknowledge financial support from R&D&I projects for international joint programming from MCIN/AEI (CONCORD, PCI2019-103436) cofunded by the European Union and from Generalitat de Catalunya (2017-SGR-1431). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya

The Interactions between Nanoparticles and the Innate Immune System from a Nanotechnologist Perspective

Inflamació; Immunitat innata; NanopartículesInflamación; Inmunidad innata; NanopartículasInflammation; Innate immunity; NanoparticlesThe immune system contributes to maintaining the body’s functional integrity through its two main functions: recognizing and destroying foreign external agents (invading microorganisms) and identifying and eliminating senescent cells and damaged or abnormal endogenous entities (such as cellular debris or misfolded/degraded proteins). Accordingly, the immune system can detect molecular and cellular structures with a spatial resolution of a few nm, which allows for detecting molecular patterns expressed in a great variety of pathogens, including viral and bacterial proteins and bacterial nucleic acid sequences. Such patterns are also expressed in abnormal cells. In this context, it is expected that nanostructured materials in the size range of proteins, protein aggregates, and viruses with different molecular coatings can engage in a sophisticated interaction with the immune system. Nanoparticles can be recognized or passed undetected by the immune system. Once detected, they can be tolerated or induce defensive (inflammatory) or anti-inflammatory responses. This paper describes the different modes of interaction between nanoparticles, especially inorganic nanoparticles, and the immune system, especially the innate immune system. This perspective should help to propose a set of selection rules for nanosafety-by-design and medical nanoparticle design.This research was funded by the EU Commission H2020 project PANDORA (GA 671881; to D.B., P.I. and V.P.). Additional funds were provided by the EU Commission H2020 project ENDONANO (GA 812661; to P.I. and D.B.), the Italian MIUR InterOmics Flagship projects MEMORAT and MAME (to D.B. and P.I.), the Italian MIUR/PRIN-20173ZECCM (to P.I.), the CAS President’s International Fellowship Programme (PIFI; award 2020VBA0028; to D.B.), Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER, UE), and Generalitat de Catalunya (2017-SGR-1431) (V.P.)

Hollow metal nanostructures for enhanced plasmonics: synthesis, local plasmonic properties and applications

Hollow nanostructures; Surface plasmon resonances (SPRs); Plasmon hybridizationNanoestructures buides; Ressonància de superfície de plasmó; Hibridació de plasmóNanoestructures vacías; Resonancia de superficie de plasmón; Hibridación de plasmónMetallic nanostructures have received great attention due to their ability to generate surface plasmon resonances, which are collective oscillations of conduction electrons of a material excited by an electromagnetic wave. Plasmonic metal nanostructures are able to localize and manipulate the light at the nanoscale and, therefore, are attractive building blocks for various emerging applications. In particular, hollow nanostructures are promising plasmonic materials as cavities are known to have better plasmonic properties than their solid counterparts thanks to the plasmon hybridization mechanism. The hybridization of the plasmons results in the enhancement of the plasmon fields along with more homogeneous distribution as well as the reduction of localized surface plasmon resonance (LSPR) quenching due to absorption. In this review, we summarize the efforts on the synthesis of hollow metal nanostructures with an emphasis on the galvanic replacement reaction. In the second part of this review, we discuss the advancements on the characterization of plasmonic properties of hollow nanostructures, covering the single nanoparticle experiments, nanoscale characterization via electron energy-loss spectroscopy and modeling and simulation studies. Examples of the applications, i.e. sensing, surface enhanced Raman spectroscopy, photothermal ablation therapy of cancer, drug delivery or catalysis among others, where hollow nanostructures perform better than their solid counterparts, are also evaluated