Understanding the Structural Parameters of Biocompatible Nanoparticles Dictating Protein Fouling

Abstract

The development of nanocarriers for biomedical applications requires that these nanocarriers have special properties, including resistance to nonspecific protein adsorption. In this study, the fouling properties of PLA- and PCL-based block copolymer nanoparticles (NPs) have been evaluated by placing them in contact with model proteins. Block copolymer NPs were produced through the self-assembly of PEOm-b-PLAn and PEOm-b-PCLn. This procedure yielded nanosized objects with distinct structural features dependent on the length of the hydrophobic and hydrophilic blocks and the volume ratio. The protein adsorption events were examined in relation to size, chain length, surface curvature, and hydrophilic chain density. Fouling by BSA and lysozyme was considerably reduced as the length of the hydrophilic PEO-stabilizing shell increases. In contrast to the case of hydrophilic polymer-grafted planar surfaces, the current investigations suggest that the hydrophilic chain density did not markedly influence protein fouling. The protein adsorption took place at the outer surface of the NPs since neither BSA nor lysozyme was able to diffuse within the hydrophilic layer due to geometric restrictions. Protein binding is an exothermic process, and it is modulated mainly by polymer features. The secondary structures of BSA and lysozyme were not affected by the adhesion phenomena.

Influence of Structural Features on the Cellular Uptake Behavior of Non-Targeted Polyester-Based Nanocarriers

“…Furthermore, NPs of higher degree of hydrophobicity (PEO‐ b ‐PCL) are more efficiently internalized as compared to PEO‐ b ‐PLA NPs. Accordingly, taking into account our recent published results and the findings of the current investigation, there should be a compromise regarding protein fouling and cellular uptake as resistance to nonspecific protein adsorption and enhanced cellular uptake are respectively directly and inversely related to the length of the PEO‐stabilizing shell.

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“…Additionally, high negative surface charge restricts cellular uptake of PLGA NPs most probably due to NP‐membrane electrostatic repulsion. Hence, and taking also into account the previously reported protein‐fouling investigations, there should be a compromise regarding protein fouling and cellular uptake since resistance to nonspecific protein adsorption and enhanced cellular uptake are respectively directly and inversely related to the length of the PEO stabilizing shell. To this end, the results suggest that the most promising candidates for intracellular drug delivery are core–shell NPs composed by a highly hydrophobic core stabilized by PEO of intermediated molecular weight.…”

Polyglycidol-Stabilized Nanoparticles as a Promising Alternative to Nanoparticle PEGylation: Polymer Synthesis and Protein Fouling Considerations

“…We have particularly measured negative -potentials for many different non-ionic particles. [35][36][37]…”

Physicochemical Study of the Interaction between Gold Nanoparticles and Lipase from Candida sp. (CALB): Insights into the Nano-Bio Interface

“…where, ε is the dielectric constant, ζ is the zeta potential (in mV), η is the viscosity and f(ka) is the Henry function, which is calculated from the Smoluchowski approximation (f(ka) = 1.5). 57 Zeta potential values are the average of five measurements.…”