Apoptotic body-inspired nanoparticles target macrophages at sites of inflammation to support an anti-inflammatory phenotype shift

Chronic inflammation is a significant pathological process found in a range of disease states. Treatments to reduce inflammation in this family of diseases may improve symptoms and disease progression, but are largely limited by variable response rates, cost, and off-target effects. Macrophages are implicated in many inflammatory diseases for their critical role in the maintenance and resolution of inflammation.

Highlights

Nanoparticles target sites of inflammation with acid-sensitive PEG shedding.

Particle uptake is inherently enriched in macrophages at the site.

An apoptotic-mimicry particle coating reduces inflammation in macrophages.

These particles may help reduce inflammation or be used as a carrier for cargo.

Macrophages exhibit significant plasticity to direct the inflammatory response by taking on an array of pro- and anti-inflammatory phenotypes based on extracellular cues. In this work, a nanoparticle has been developed to target sites of inflammation and reduce the inflammatory macrophage phenotype by mimicking the anti-inflammatory effect of apoptotic cell engulfment. The nanoparticle, comprised of a poly(lactide-co-glycolide) core, is coated with phosphatidylserine (PS)-supplemented cell plasma membrane to emulate key characteristics of the apoptotic cell surface. The particle surface is additionally functionalized with an acid-sensitive sheddable polyethylene glycol (PEG) moiety to increase the delivery of the nanoparticles to low pH environments such as those of chronic inflammation.

In a mouse model of lipopolysaccharide-induced inflammation, particles were preferentially taken up by macrophages at the site and promoted an anti-inflammatory phenotype shift. This PEGylated membrane coating increased the delivery of nanoparticles to sites of inflammation and may be used as a tool alone or as a delivery scheme for additional cargo to reduce macrophage-associated inflammatory response.

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Article information: Chelsea A. Kraynak, Wenbai Huang, Elizabeth C. Bender, Jie-Liang Wang, Mahmoud S. Hanafy, Zhengrong Cui, Laura J. Suggs, Apoptotic body-inspired nanoparticles target macrophages at sites of inflammation to support an anti-inflammatory phenotype shift, International Journal of Pharmaceutics, Volume 618, 2022, 121634, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2022.121634.