The effect of polymer coating on nanoparticles' interaction with lipid membranes studied by coarse-grained molecular dynamics simulations.

Nanoparticles' (NPs) permeation through cell membranes, whether it happens passive or active transport, is an essential initial step for their cellular internalization. The NPs' surface coating impacts the way they translocate through the lipid bilayer and the spontaneity of the process. Understanding the molecular details of NPs' interaction with cell membranes allows the design of nanosystems with optimal characteristics for crossing the lipid bilayer: computer simulations are a powerful tool for this purpose.

Mechanism of RGD-conjugated nanodevice binding to its target protein integrin αβ by atomistic molecular dynamics and machine learning.

Active targeting strategies have been proposed to enhance the selective uptake of nanoparticles (NPs) by diseased cells, and recent experimental findings have proven the effectiveness of this approach. However, no mechanistic studies have yet revealed the atomistic details of the interactions between ligand-activated NPs and integrins. As a case study, here we investigate, by means of advanced molecular dynamics simulations (MD) and machine learning methods (namely equilibrium MD, binding free energy calculations and training of self-organized maps), the interaction of a cyclic-RGD-conjugated PEGylated TiO NP (the nanodevice) with the extracellular segment of integrin αβ (the target), the latter experimentally well-known to be over-expressed in several solid tumors.

Molecular Dynamics for the Optimal Design of Functionalized Nanodevices to Target Folate Receptors on Tumor Cells.

Atomistic details on the mechanism of targeting activity by biomedical nanodevices of specific receptors are still scarce in the literature, where mostly ligand/receptor pairs are modeled. Here, we use atomistic molecular dynamics (MD) simulations, free energy calculations, and machine learning approaches on the case study of spherical TiO nanoparticles (NPs) functionalized with folic acid (FA) as the targeting ligand of the folate receptor (FR). We consider different FA densities on the surface and different anchoring approaches, i.

Modeling Zeta Potential for Nanoparticles in Solution: Water Flexibility Matters.

Nonequilibrium molecular dynamics simulations were performed to study the electrokinetic properties of five mainstream TIPP water models (namely, TIP3P-FB, TIP3Pm, TIP4P-FB, TIP4P-Ew, and TIP4P/2005) in NaCl aqueous solutions in the presence of a negatively charged TiO surface. The impact of solvent flexibility and system geometry on the electro-osmotic (EO) mobility and flow direction was systematically assessed and compared. We found that lack of water flexibility decelerates the forward EO flow of aqueous solutions at moderate (0.

Metadynamics simulations for the investigation of drug loading on functionalized inorganic nanoparticles.

Inorganic nanoparticles show promising properties that allow them to be efficiently used as drug carriers. The main limitation in this type of application is currently the drug loading capacity, which can be overcome with a proper functionalization of the nanoparticle surface. In this study, we present, for the first time, a computational approach based on metadynamics to estimate the binding free energy of the doxorubicin drug (DOX) to a functionalized TiO nanoparticle under different pH conditions.

Multi-scale modeling of folic acid-functionalized TiO nanoparticles for active targeting of tumor cells.

Strategies based on the active targeting of tumor cells are emerging as smart and efficient nanomedical procedures. Folic acid (FA) is a vitamin and a well-established tumor targeting agent because of its strong affinity for the folate receptor (FR), which is an overexpressed protein on the cell membranes of the tumor cells. FA can be successfully anchored to several nanocarriers, including inorganic nanoparticles (NPs) based on transition metal oxides.

Molecular dynamics simulations of cRGD-conjugated PEGylated TiO nanoparticles for targeted photodynamic therapy.

The conjugation of high-affinity cRGD-containing peptides is a promising approach in nanomedicine to efficiently reduce off-targeting effects and enhance the cellular uptake by integrin-overexpressing tumor cells. Herein we utilize atomistic molecular dynamics simulations to evaluate key structural-functional parameters of these targeting ligands for an effective binding activity towards αβ integrins. An increasing number of cRGD ligands is conjugated to PEG chains grafted to highly curved TiO nanoparticles to unveil the impact of cRGD density on the ligand's presentation, stability, and conformation in an explicit aqueous environment.

Effect of dopamine-functionalization, charge and pH on protein corona formation around TiO nanoparticles.

Inorganic nanoparticles (NPs) are gaining increasing attention in nanomedicine because of their stimuli responsiveness, which allows combining therapy with diagnosis. However, little information is known about their interaction with intracellular or plasma proteins when they are introduced in a biological environment. Here we present atomistic molecular dynamics (MD) simulations investigating the case study of dopamine-functionalized TiO nanoparticles and two proteins that are overexpressed in cancer cells, PARP1 and HSP90, since experiments proved them to be the main components of the corona in cell cultures.

Molecular dynamics simulations of doxorubicin in sphingomyelin-based lipid membranes.

Doxorubicin (DOX) is one of the most efficient antitumor drugs employed in numerous cancer therapies. Its incorporation into lipid-based nanocarriers, such as liposomes, improves the drug targeting into tumor cells and reduces drug side effects. The carriers' lipid composition is expected to affect the interactions of DOX and its partitioning into liposomal membranes.

Exploring the drug loading mechanism of photoactive inorganic nanocarriers through molecular dynamics simulations.

Inorganic nanoparticles are gaining increasing attention as drug carriers because they respond to external physical stimuli, allowing therapy to be combined with diagnosis. Their drawback is low drug loading capacity, which can be improved by proper and efficacious functionalization. In this computational study, we take TiO spherical nanoparticles as prototype photoresponsive inorganic nanoparticles and we fully decorate them with two different types of bifunctional ligands: TETTs and DOPACs, which present different surface anchoring groups (silanol or catechol) but the same drug tethering COOH group, although in different concentrations (3 vs.

Multiscale simulations of the hydration shells surrounding spherical FeO nanoparticles and effect on magnetic properties.

Iron oxide magnetic nanoparticles (NPs) are excellent systems in catalysis and in nanomedicine, where they are mostly immersed in aqueous media. Even though the NP solvation by water is expected to play an active role, the detailed structural insight at the nanostructure oxide/water interface is still missing. Here, based on our previous efforts to obtain accurate models of dehydrated Fe3O4 NPs and of their magnetic properties and through multiscale molecular dynamics simulations combining the density functional tight binding method and force field, we unravel the atomistic details of the short range (chemical) and long range (physical) interfacial effects when magnetite nanoparticles are immersed in water.

Parametrization of the Fe-O cross-interaction for a more accurate FeO/water interface model and its application to a spherical FeO nanoparticle of realistic size.

The accurate description of iron oxides/water interfaces requires reliable force field parameters that can be developed through comparison with sophisticated quantum mechanical calculations. Here, a set of CLASS2 force field parameters is optimized to describe the Fe-O cross-interaction through comparison with hybrid density functional theory (HSE06) calculations of the potential energy function for a single water molecule adsorbed on the FeO (001) surface and with density functional tight binding (DFTB+U) molecular dynamics simulations for a water trilayer on the same surface. The performance of the new parameters is assessed through the analysis of the number density profile of a water bulk (12 nm) sandwiched between two magnetite slabs of large surface area.

Dopamine-Decorated TiO Nanoparticles in Water: A QM/MM vs an MM Description.

Nanoparticle functionalization is a modern strategy in nanotechnology to build up devices for several applications. Modeling fully decorated metal oxide nanoparticles of realistic size (few nanometers) in an aqueous environment is a challenging task. In this work, we present a case study relevant for solar-light exploitation and for biomedical applications, i.

Insight into the interface between FeO (001) surface and water overlayers through multiscale molecular dynamics simulations.

In this work, we investigate the FeO (001) surface/water interface by combining several theoretical approaches, ranging from a hybrid functional method (HSE06) to density-functional tight-binding (DFTB) to molecular mechanics (MM). First, we assess the accuracy of the DFTB method to correctly reproduce HSE06 results on structural details and energetics and available experimental data for adsorption of isolated water, dimers, and trimers up to a water monolayer. Second, we build two possible configurations of a second and a third overlayer and perform molecular dynamics simulations with DFTB, monitoring the water orientation, the H-bond network, and the ordered water structure formation.

Parallel damage in mitochondria and lysosomes is an efficient way to photoinduce cell death.

Cells challenged by photosensitized oxidations face strong redox stresses and rely on autophagy to either survive or die. However, the use of macroautophagy/autophagy to improve the efficiency of photosensitizers, in terms of inducing cell death, remains unexplored. Here, we addressed the concept that a parallel damage in the membranes of mitochondria and lysosomes leads to a scenario of autophagy malfunction that can greatly improve the efficiency of the photosensitizer to cause cell death.