Hydrogel nanoparticle degradation influences the activation and survival of primary macrophages
| Author(s) | Jarai, Bader M. | |
| Author(s) | Stillman, Zachary | |
| Author(s) | Fromen, Catherine A. | |
| Date Accessioned | 2022-01-26T21:01:54Z | |
| Date Available | 2022-01-26T21:01:54Z | |
| Publication Date | 2021-06-28 | |
| Description | This article was originally published in Journal of Materials Chemistry B. The version of record is available at: https://doi.org/10.1039/D1TB00982F | en_US |
| Abstract | The effect of nanoparticle (NP) internalization on cell fate has emerged as an important consideration for nanomedicine design, as macrophages and other phagocytes are the primary clearance mechanisms of administered NP formulations. Pro-survival signaling is thought to be concurrent with phagocytosis and recent work has shown increased macrophage survival following lysosomal processing of internalized NPs. These observations have opened the door to explorations of NP physiochemical properties aimed at tuning the NP-driven macrophage survival at the lysosomal synapse. Here, we report that NP-induced macrophage survival and activation is strongly dependent on NP degradation rate using a series of thiol-containing poly(ethylene glycol) diacrylate-based NPs of equivalent size and zeta potential. Rapidly degrading, high thiol-containing NPs allowed for dramatic enhancement of cell longevity that was concurrent with macrophage stimulation after 2 weeks in ex vivo culture. While equivalent NP internalization resulted in suppressed caspase activity across the NP series, macrophage activation was correlated with increasing thiol content, leading to increased lysosomal activity and a robust pro-survival phenotype. Our results provide insight on tuning NP physiochemical properties as design handles for maximizing ex vivo macrophage longevity, which has implications for improving macrophage-based immune assays, biomanufacturing, and cell therapies. | en_US |
| Sponsor | Research reported in this publication was supported by the National Institutes of Health and the State of Delaware under Award Number P20GM103446 and P20GM104316, as well as a Research Starter Grant in Pharmaceutics from the PhRMA Foundation, and a University of Delaware Research Foundation Award. Z. S. S. was supported by a T32GM008550 training grant. Thermo Scientific™ Apreo VS SEM microscope equipment was acquired with a shared instrumentation grant (S10 OD025165) and access was supported by the NIH-NIGMS (P20 GM103446), the NSF (IIA-1301765) and the State of Delaware. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. | en_US |
| Citation | Jarai, Bader M., Zachary Stillman, and Catherine A. Fromen. 2021. “Hydrogel Nanoparticle Degradation Influences the Activation and Survival of Primary Macrophages.” J. Mater. Chem. B 9 (35): 7246–57. https://doi.org/10.1039/D1TB00982F. | en_US |
| ISSN | 2050-7518 | |
| URL | https://udspace.udel.edu/handle/19716/30126 | |
| Language | en_US | en_US |
| Publisher | Journal of Materials Chemistry B | en_US |
| Title | Hydrogel nanoparticle degradation influences the activation and survival of primary macrophages | en_US |
| Type | Article | en_US |
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