Apoptotic body-inspired nanoparticles target macrophages at sites of inflammation to support an anti-inflammatory
Chelsea A Kraynak1, Wenbai Huang2, Elizabeth C Bender1
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Abstract:
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. 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.
Insights
Researchers developed novel nanoparticles that mimic apoptotic cells to reduce chronic inflammation by reprogramming macrophages. These targeted nanoparticles show promise for treating inflammatory diseases with fewer side effects.
Area of Science:
- Biomaterials Science
- Immunology
- Nanotechnology
Background:
- Chronic inflammation underlies numerous diseases, with current treatments facing limitations like variable efficacy and side effects.
- Macrophages play a crucial role in inflammation, exhibiting plasticity to adopt pro- or anti-inflammatory phenotypes based on environmental signals.
Purpose of the Study:
- To develop a nanoparticle-based therapeutic strategy to target and modulate macrophages at inflammatory sites.
- To mimic the natural anti-inflammatory effects of apoptotic cell engulfment for therapeutic benefit.
Main Methods:
- Engineered nanoparticles with a poly(lactide-co-glycolide) core coated in phosphatidylserine (PS)-supplemented cell plasma membrane.
- Functionalized nanoparticle surface with an acid-sensitive, sheddable polyethylene glycol (PEG) moiety for enhanced delivery to acidic inflammatory environments.
- Evaluated nanoparticle uptake and effects on macrophage phenotype in a lipopolysaccharide-induced mouse inflammation model.
Main Results:
- Nanoparticles were preferentially phagocytosed by macrophages at the site of inflammation.
- The engineered nanoparticles successfully induced a shift towards an anti-inflammatory macrophage phenotype.
- The PEGylated coating enhanced nanoparticle delivery to inflammatory loci.
Conclusions:
- The developed nanoparticles effectively target macrophages and promote an anti-inflammatory phenotype shift, offering a novel therapeutic approach.
- This nanoparticle system, particularly with the PEGylated coating, enhances delivery to inflammatory sites and holds potential for treating macrophage-associated inflammatory conditions.
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