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

Alexandra S. Piotrowski-Daspit (), Laura G. Bracaglia (), David A. Eaton, Owen Richfield, Thomas C. Binns, Claire Albert, Jared Gould, Ryland D. Mortlock, Marie E. Egan, Jordan S. Pober and W. Mark Saltzman ()
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Alexandra S. Piotrowski-Daspit: Yale University
Laura G. Bracaglia: Yale University
David A. Eaton: Yale University
Owen Richfield: Yale University
Thomas C. Binns: Yale University
Claire Albert: Yale University
Jared Gould: Yale University
Ryland D. Mortlock: Yale University
Marie E. Egan: Yale School of Medicine
Jordan S. Pober: Yale School of Medicine
W. Mark Saltzman: Yale University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-48442-7

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