Quantifying Vascular Distribution and Adhesion of Nanoparticles with Protein Corona in Microflow

Abstract

The protein corona has emerged as an important determinant of biological response in nanoparticle (NP) drug delivery. However, there is presently no reported study on how the protein corona affects the behavior of NPs in microflow and its subsequent interactions with the vascular endothelium, which could affect their delivery to the target tumor site regardless of its targeting mechanism. Furthermore, a consensus on the role of physical and surface characteristics of NPs in affecting the margination of NPs is lacking due to different methods of quantifying margination. In this study, we examine how the particle adhesion (PA) method and particle distribution (PD) method quantify the margination of 20, 40, 100, and 200 nm polystyrene NPs (pNPs) differently in fibronectin or pluronic F-127-coated microfluidic straight channels. We found that PA reduced with increasing pNP size, whereas the PD was similar across all pNP sizes regardless of channel coating. We then formed a protein corona on all pNPs (pNPs-PC) and found that the protein corona increased the adhesion of 40-200 nm pNPs in fibronectin-coated channels, with no size dependence between them except for 40 nm, which had significantly higher particle adhesion. The PA method was also dependent on channel coating, whereas the PD method was independent of channel coating. These results suggested that the PA method was more amenable to surface interactions between the pNPs and the channel wall while providing a measure of the amount of NPs that interacted with the channel walls, whereas the PD method provided a representation of their distribution across the channel due to margination. The two methods complement each other to elucidate a more holistic understanding of how different factors might affect a NP's margination in future studies.

Probing cell–nanoparticle (cubosome) interactions at the endothelial interface: do tissue dimension and flow matter?

“…migration towards the wall) of nanoparticles under flow conditions via the formation of protein corona, leukocyte-assisted trafficking as well as through alteration of the ratio between inertial and Brownian forces. 8,40,44,46,47 Furthermore, PHY (being a fusogenic lipid) may undergo competitive interactions between the blood and tissue cells. Numerous previous studies have shown that PHY-based nanoparticles are capable of exerting extensive hemolytic action at 10-times lower concentrations than that causing tissue cytotoxicity, even in the presence of Poloxamers (ranging between 3-30 % w/w).…”

Cyclical endometrial repair and regeneration: Molecular mechanisms, diseases, and therapeutic interventions

“…Its hydrophilic and lipophilic properties, combined with its capacity for self‐organizing micelles, render it suitable for drug delivery 338 . Additionally, it finds extensive application in piggyback cells, 339 proteins, 340 growth factors, 341 and so on. Poloxamer 188, poloxamer 127, poloxamer 237, and poloxamer 407 are frequently used in biomedical engineering 334,342–345 .…”

Challenges and Opportunities of Nanotechnology as Delivery Platform for Tocotrienols in Cancer Therapy

“…In recent years, computational methods or simulated tools to obtain detailed view of nanocarriers-organs interactions during their transport to tumors have become increasingly popular. Kiew et al (2017) and Ho et al (2018) investigated the permeability of nanocarriers in vitro using biomimetic microfluidic models. These techniques enabled preliminary assessment on the delivery efficiency of nanocarriers, which can provide a feedback system to formulation studies.…”