Core, Coating, or Corona? The Importance of Considering Protein Coronas in nano-QSPR Modeling of Zeta Potential

Abstract

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.

High-Performance Fluorescent Microspheres Based on Fluorescence Resonance Energy Transfer Mode for Lateral Flow Immunoassays

“…The dynamic light scattering (DLS) analysis revealed that the average hydration size of DAIEPMs (235.4 nm; Figure D) was slightly larger than that of AIEPMs (182 nm; Figure E) and increased with an increasing concentration of TCBPEME (Figure S2), which is probably caused by the loading of more AIEgens into the microspheres. The zeta potential analysis showed that the surface charges of DAIEPMs (−51 mV; Figure F) and BAPFPMs (−47.53 mV; Figure F) were negative, demonstrating their good dispersion stability in aqueous solutions . The absorption intensities of DAIEPMs ranged from 300 to 400 nm and were considerably higher than those of BAPFPMs; moreover, the characteristic absorption peak at 520 nm was retained, which may verify the simultaneous loading of the two AIEgens (Figure G).…”

“…The zeta potential analysis showed that the surface charges of DAIEPMs (−51 mV; Figure 2F) and BAPFPMs (−47.53 mV; Figure 2F) were negative, demonstrating their good dispersion stability in aqueous solutions. 28 The absorption intensities of DAIEPMs ranged from 300 to 400 nm and were considerably higher than those of BAPFPMs; moreover, the characteristic absorption peak at 520 nm was retained, which may verify the simultaneous loading of the two AIEgens (Figure 2G).…”

Ephedra intermedia Schrenk & C. A. Mey Methanol Extract: Nanoencapsulation by Mini‐Emulsion Polymerization and its Release Trend under Simulated Conditions of the Human Body

“…The average particle size distribution in this study was 47 nm, which is optimal for passing through biological cells. The zeta potential is an important parameter that reflects the physicochemical properties and biological stability of produced nanoparticles [93–95] . It is used to measure the surface charge and, consequently, the stability of nanoparticles [96] .…”

“…The zeta potential is an important parameter that reflects the physicochemical properties and biological stability of produced nanoparticles. [93][94][95] It is used to measure the surface charge and, consequently, the stability of nanoparticles. [96] The zeta potential of the encapsulated E. intermedia extract was found to be 33 mV, while the same parameter was reported to be 12 mV for the liposomal extract of green tea.…”

Toward Nano‐Specific In Silico NAMs: How to Adjust Nano‐QSAR to the Recent Advancements of Nanotoxicology?

“…Although this approach is still in its infancy, a recently proposed model considers the protein corona assessment for the prediction of the zeta potential of ENMs. [40] Figure 3. The toxicity of NPs on the gastrointestinal tract.…”