Modulation of Macrophage Phenotype by Biodegradable Polyurethane Nanoparticles: Possible Relation between Macrophage Polarization and Immune Response of Nanoparticles

Abstract

Nanomaterials with surface functionalized by different chemical groups can either provoke or attenuate the immune responses of the nanomaterials, which is critical to their biomedical efficacies. In this study, we demonstrate that synthetic waterborne polyurethane nanoparticles (PU NPs) can inhibit the macrophage polarization toward the M1 phenotype but not M2 phenotype. The surface-functionalized PU NPs decrease the secretion levels of proinflammatory cytokines (TNF-α and IL-1β) for M1 macrophages. Specifically, PU NPs with carboxyl groups on the surface exhibit a greater extent of inhibition on M1 polarization than those with amine groups. These water-suspended PU NPs reduce the nuclear factor-κB (NF-κB) activation and suppress the subsequent NLR family pyrin domain containing 3 (NLRP3) inflammasome signals. Furthermore, the dried PU films assembled from PU NPs have a similar effect on macrophage polarization and present a smaller shifting foreign body reaction (FBR) in vivo than the conventional poly(l-lactic acid). Taken together, the biodegradable waterborne PU NPs demonstrate surface-dependent immunosuppressive properties and macrophage polarization effects. The findings suggest potential therapeutic applications of PU NPs in anti-inflammation and macrophage-related disorders and propose a mechanism for the low FBR observed for biodegradable PU materials.

Self‐Healing Hydrogels and Cryogels from Biodegradable Polyurethane Nanoparticle Crosslinked Chitosan

“…There was no significant difference in the M2/M1 ratio between CS‐PU cryogel and PU film. Both groups had an M2/M1 ratio of about 3, higher than that (about 0.5) reported for polylactide …”

“…These data indicated that CS‐PU cryogel was superior to the conventional PLA in biocompatibility. Polyurethane nanoparticles and films were reported to inhibit the macrophage polarization toward the M1 phenotype . The good individual biocompatibility of PU and CS may explain the low immune reaction of the CS‐PU cryogel.…”

The Histological Composition of Capsular Contracture Focussed on the Inner Layer of the Capsule: An Intra-Donor Baker-I Versus Baker-IV Comparison

“…This repeated exposure of the implant to stress could be the start of a more, secondary, profibrotic process. The macrophage seems to be susceptible to modulation and has already been suggested as a target for a therapeutic approach to prevent capsular contraction [ 33 ]. Our results indicate only a slight increase in CD68 positivity in the outer layers of the Baker-IV capsules, and therefore, it is likely that one or more other types of immune cells, like different T-cell subsets, are also involved in this process [ 34 ].…”

Spatially Resolved Correlation between Stiffness Increase and Actin Aggregation around Nanofibers Internalized in Living Macrophages

“…Drug treatment is one of the most important approaches to achieve macrophage functionalization [ 3 ], and in addition to the widely used chemical drugs, nanomedicines are attractive due to their controlled drug release, prolonged half-life and lower side effects [ 4 ]. Indeed, nanoparticles have been used in therapeutic applications of anti-inflammation and macrophage-related disorders [ 5 ] and to inhibit tumor growth by inducing pro-inflammatory macrophage polarization [ 6 ]. In some cases, however, macrophages mutate into a pro-healing phenotype, resulting in tumor-associated macrophages (TAMs) that promote the metastasis, shifting tumors towards an immunosuppressive microenvironment, and thus increasing the resistance to cancer therapy [ 7 ].…”