(595b) Soft Poly-Ethylene-Glycol (PEG) Micelles and Lipid Nanoparticles (LNPs) Resolve Autophagy and Reduce Pro-Inflammatory Cytokine Secretion in RAW264.7 Murine Macrophages

The effects of soft poly-ethylene-glycol (PEG)-based nanoparticles (NPs) on macrophage autophagy and inflammatory signaling are largely unknown. With the prevalent use of PEG NPs that are lipid nanoparticles (LNPs) as vaccine adjuvants, drug delivery vehicles, and carriers of nucleic acid reagents, it is crucial to understand how they affect these two pathways. Here, we show that soft PEG-poly-butadiene (PEG-PBD) cylindrical and spherical micelle nanoparticles (CNPs and SNPs), and lipid nanoparticles (LNPs) that have the lipid makeup of the chemotherapy carrier DOXIL lower murine RAW264.7 macrophage autophagosome abundance over 24 hours of incubation. CNPs, SNPs, and LNPs mostly resolve autophagosome formation triggered by starvation, rapamycin, and lipopolysaccharide (LPS). All three PEG NPs lower autophagosome abundance when macrophages are cultured in serum from obese humans. CNPs, SNPs, and LNPs lower reactive oxygen species (ROS) in macrophages. Surprisingly, all the three PEG NPs – especially LNPs - decreased the levels of most of the macrophage cytokines compared to controls over 24-hour incubations. Our findings show that soft PEG NPs do not augment autophagy or inflammation like many hard NPs. Instead, they resolve macrophage autophagy and reduce inflammation. Also, macrophages seem to treat PEG NPs like lipoproteins, not foreign objects. Thus, the terminology that macrophages “clear” PEG NPs, which has been used over many decades, is misleading.