Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys.

Autor: Piotrowski-Daspit AS; Department of Biomedical Engineering, Yale University, New Haven, CT, US. asapd@umich.edu.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, US. asapd@umich.edu.; Department of Internal Medicine - Pulmonary and Critical Care Medicine Division, Michigan Medicine, University of Michigan, Ann Arbor, MI, US. asapd@umich.edu., Bracaglia LG; Department of Biomedical Engineering, Yale University, New Haven, CT, US. laura.bracaglia@villanova.edu.; Department of Chemical and Biological Engineering, Villanova University, Villanova, PA, US. laura.bracaglia@villanova.edu., Eaton DA; Department of Biomedical Engineering, Yale University, New Haven, CT, US., Richfield O; Department of Biomedical Engineering, Yale University, New Haven, CT, US., Binns TC; Department of Biomedical Engineering, Yale University, New Haven, CT, US.; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, US., Albert C; Department of Biomedical Engineering, Yale University, New Haven, CT, US., Gould J; Department of Biomedical Engineering, Yale University, New Haven, CT, US., Mortlock RD; Department of Biomedical Engineering, Yale University, New Haven, CT, US., Egan ME; Department of Pediatrics, Yale School of Medicine, New Haven, CT, US.; Department of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, US., Pober JS; Department of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, US.; Department of Immunobiology, Yale School of Medicine, New Haven, CT, US., Saltzman WM; Department of Biomedical Engineering, Yale University, New Haven, CT, US. mark.saltzman@yale.edu.; Department of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, US. mark.saltzman@yale.edu.; Department of Dermatology, Yale School of Medicine, New Haven, CT, US. mark.saltzman@yale.edu.; Department of Chemical & Environmental Engineering, Yale University, New Haven, CT, US. mark.saltzman@yale.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 18; Vol. 15 (1), pp. 4247. Date of Electronic Publication: 2024 May 18.
DOI: 10.1038/s41467-024-48442-7
Abstrakt: The in vivo efficacy of polymeric nanoparticles (NPs) is dependent on their pharmacokinetics, including time in circulation and tissue tropism. Here we explore the structure-function relationships guiding physiological fate of a library of poly(amine-co-ester) (PACE) NPs with different compositions and surface properties. We find that circulation half-life as well as tissue and cell-type tropism is dependent on polymer chemistry, vehicle characteristics, dosing, and strategic co-administration of distribution modifiers, suggesting that physiological fate can be optimized by adjusting these parameters. Our high-throughput quantitative microscopy-based platform to measure the concentration of nanomedicines in the blood combined with detailed biodistribution assessments and pharmacokinetic modeling provides valuable insight into the dynamic in vivo behavior of these polymer NPs. Our results suggest that PACE NPs-and perhaps other NPs-can be designed with tunable properties to achieve desired tissue tropism for the in vivo delivery of nucleic acid therapeutics. These findings can guide the rational design of more effective nucleic acid delivery vehicles for in vivo applications.
(© 2024. The Author(s).)
Databáze: MEDLINE
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