2 research outputs found
Quantifying Vascular Distribution and Adhesion of Nanoparticles with Protein Corona in Microflow
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
presentation_1_Characterizing the Role of Monocytes in T Cell Cancer Immunotherapy Using a 3D Microfluidic Model.PDF
<p>In the hepatitis B virus (HBV)-related hepatocellular carcinoma tumor microenvironment (TME), monocytes reportedly impede natural T cell functions via PD-L1/PD-1 signaling. However, it remains unclear if T cell receptor-redirected T cells (TCR T cells) are similarly inhibited. Hence, we developed a 3D intrahepatic TME microfluidic model to investigate the immunosuppressive potential of monocytes toward HBV-specific TCR T cells and the role of PD-L1/PD-1 signaling. Interestingly, in our 3D static microfluidic model, we observed that monocytes suppressed only retrovirally transduced (Tdx) TCR T cell cytotoxicity toward cancer cells via PD-L1/PD-1, while mRNA electroporated (EP) TCR T cell cytotoxicity was not affected by the presence of monocytes. Importantly, when co-cultured in 2D, both Tdx and EP TCR T cell cytotoxicity toward cancer cells were not suppressed by monocytes, suggesting our 3D model as a superior tool compared to standard 2D assays for predicting TCR T cell efficacy in a preclinical setting, which can thus be used to improve current immunotherapy strategies.</p