To control stability in a biological medium, several factors affecting the zeta potential (ζ) of nanoparticles (NPs) must be considered, including complex interactions between the nanostructure and the composition of the protein corona (PC). Effective in silico methods (based on machine learning and quantitative structure–property relationship (QSPR) models) could help predict and characterize the relationship between the physicochemical properties of NP and the formation of PC and biological outcomes in the medium at an early stage of the experiment. However, the models currently developed are limited to simple descriptors that do not represent the complex interactions between the core, the coating, and their PC fingerprints. To be useful, the models developed should be described as a function of both the structural properties determined by the core and coating of the NPs and the biological medium determined by the formation of the protein corona. We have developed a set of complex descriptors that describe the quantitative relationship between the value of the zeta potential (ζ), core, the coating of NPs, and their PC fingerprints (the so-called nano-QSPR model). The nano-QSPR model was developed based on a genetic algorithm using a partial least-squares regression method (GA-PLS), which is characterized by high external predictive power (Q 2 EXT = 0.89). The GA-PLS model was developed using descriptors that describe (i) the core structure (determined by 7 different types of polymer-based NMs in the range of 20 different sizes), (ii) the coating structure with 7 different functional groups, and (iii) 80 different types of protein compositions adsorbed on the surface of the NPs. The presented study answers the question of how complex interactions between the corona and NP determine the zeta potential (ζ) of NP in a given medium. Moreover, our current study is a proof-of-concept that the zeta potential of NPs modeled on the original structure depends not only on the NPs themselves but also on the structure and properties determined by the NP core and coating, as well as the biological medium determined by the formation of the protein corona. On the basis of these results, our studies will be useful in determining the stability and mechanism of cell uptake, toxicity, and ability to predict the zeta potential of compounds not yet tested.

This work aimed to investigate the interaction of bovine serum albumin with newly synthesized potent new pyrene derivatives (PS1 and PS2), which might prove useful to have a better antibacterial character as found for similar compounds in the previous report [ Bioconjugate Chemistry 2014 12 2269 2284 ]. However, to date, binding studies with plasma protein are still unknown. Steady-state fluorescence spectroscopy and lifetime fluorescence studies show that the static interaction binding mode and binding constants of PS1 and PS2 are 7.39 and 7.81 [ K b × 10 5 (M –1 )], respectively. The experimental results suggest that hydrophobic forces play a crucial role in interacting pyrene derivatives with BSA protein. To verify this, molecular docking and molecular dynamics simulations were performed to predict the nature of the interaction and the dynamic behavior of the two compounds in the BSA complex, PS1 and PS2, under physiological conditions of pH = 7.1. In addition, the free energies of binding for the BSA-PS1 and BSA-PS2 complexes were estimated at 300 K based on the molecular mechanics of the Poisson–Boltzmann surface (MMPBSA) with the Gromacs package. PS2 was found to have a higher binding affinity than PS1. To determine the behavior of the orbital transitions in the ground state geometry, we found that both compounds have similar orbital transitions from HOMO–LUMO via π → π* and HOMO–1–LUMO+1 via n → π*, which was included in the FMO analysis. A cytotoxicity study was performed to determine the toxicity of the compounds. Based on the MD study, the stability of the compounds with BSA and the dynamic binding modes were further revealed, as well as the nature of the binding force components involved and the important residues involved in the binding process. From the binding energy analysis, it can be assumed that PS2 may be more active than PS1.

The lack of knowledge about the uptake of NPs by biological cells poses a significant problem for drug delivery. For this reason, designing an appropriate model is the main challenge for modelers. To address this problem, molecular modeling studies that can describe the mechanism of cellular uptake of drug-loaded nanoparticles have been conducted in recent decades. In this context, we developed three different models for the amphipathic nature of drug-loaded nanoparticles (MTX-SS-γ-PGA), whose cellular uptake mechanism was predicted by molecular dynamics studies. Many factors affect nanoparticle uptake, including nanoparticle physicochemical properties, protein–particle interactions, and subsequent agglomeration, diffusion, and sedimentation. Therefore, the scientific community needs to understand how these factors can be controlled and the NP uptake of nanoparticles. Based on these considerations, in this study, we investigated for the first time the effects of the selected physicochemical properties of the anticancer drug methotrexate (MTX) grafted with hydrophilic-γ-polyglutamic acid (MTX-SS-γ-PGA) on its cellular uptake at different pH values. To answer this question, we developed three theoretical models describing drug-loaded nanoparticles (MTX-SS-γ-PGA) at three different pH values, such as (1) pH 7.0 (the so-called neutral pH model), (2) pH 6.4 (the so-called tumor pH model), and (3) pH 2.0 (the so-called stomach pH model). Exceptionally, the electron density profile shows that the tumor model interacts more strongly with the head groups of the lipid bilayer than the other models due to charge fluctuations. Hydrogen bonding and RDF analyses provide information about the solution of the NPs with water and their interaction with the lipid bilayer. Finally, dipole moment and HOMO-LUMO analysis showed the free energy of the solution in the water phase and chemical reactivity, which are particularly useful for determining the cellular uptake of the NPs. The proposed study provides fundamental insights into molecular dynamics (MD) that will allow researchers to determine the influence of pH, structure, charge, and energetics of NPs on the cellular uptake of anticancer drugs. We believe that our current study will be useful in developing a new model for drug delivery to cancer cells with a much more efficient and less time-consuming model.

In this work, we have employed an intramolecular charge transfer-based DMN colorimetric probe for the rapid naked-eye detection of cyanide ions in solution as well as real water samples. The...

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