Effect of the Poly(ethylene glycol) (PEG) Density on the Access and Uptake of Particles by Antigen-Presenting Cells (APCs) after Subcutaneous Administration

Abstract

Lymphatic trafficking of particles to the secondary lymphoid organs, such as lymph nodes, and the cell types that particles access are critical factors that control the quality and quantity of immune responses. In this study, we evaluated the effect of PEGylation on the lymphatic trafficking and accumulation of particles in draining lymph nodes (dLNs) as well as the cell types that internalized particles. As a model system, 200 nm polystyrene (PS) particles were modified with different densities of poly(ethylene glycol) (PEG) and administered subcutaneously to mice. PEGylation enhanced the efficiency of particle drainage away from the injection site as well as the access of particles to dendritic cells (DCs). The accumulation of particles in dLNs was dependent on the PEG density. PEGylation also enhanced uptake by DCs while reducing internalization by B cells at the single cell level. Our results indicate that PEGylation facilitated the trafficking of particles to dLNs either through enhanced trafficking in lymphatic vessels or by enhanced internalization by migratory DCs. This study provides insight into utilizing PEGylated particles for the development of synthetic vaccines.

PEGylation of interferon α2 improves lymphatic exposure after subcutaneous and intravenous administration and improves antitumour efficacy against lymphatic breast cancer metastases

“…The data therefore suggest that by improving the exposure of lymphocytes and NK cells in lymph nodes and the lymphatic system to interferon, the anti-cancer activity of the protein may be enhanced against lymph-resident cancers. This suggestion is consistent with the vaccine literature which indicates that improving the lymphatic disposition of vaccines significantly augments the immune response by better exposing the antigen to antigen presenting cells and naïve T cells[33]. …”

Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

“…BCT-100 may be internalized by AML blasts, consistent with other PEG molecules in myeloid cells, which would further contribute to low intracellular arginine concentrations. 46 BCT-100 can work in combination with cytarabine. Cytarabine in its triphosphorylated form is a substrate for DNA polymerases and is incorporated into phosphodiester linkages in the DNA strand.…”

PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

“…The authors speculate that the PEG-PDMAEMA polymer also had some adjuvant properties that contributed to the immune response in vivo [183]. Zhan and coworkers explored the effect of PEG coatings on NP drainage to the lymph nodes and access and uptake of NPs by APCs after subcutaneous administration [184]. They used 200 nm carboxylate-modified PS NPs as fluorescent probes and conjugated 5 kDa PEG at varying amounts to the NP surface; the size and ζ-potential of the NPs increased as the PEG surface density increased.…”

“…Interestingly, PEGylation also increased the amount of NPs internalized by all four dendritic cell subsets examined. The authors speculated that although PEGylation of NPs reduces cellular uptake by phagocytic cells in vitro , the relative increase in the amount of PEGylated NPs that reached the draining lymph nodes may have resulted in the relative increase in uptake [184]. Xie and coworkers explored PEG modification of recombinant adenoviral (rAd) vectors to overcome the vaginal mucus barrier for improved vaginal vaccination [185].…”