A new biomimetic drug delivery system consisting of nanoparticles that are coated with macrophage membrane and responsive to reactive oxygen species (ROS) enables targeted pharmacotherapy for atherosclerosis in mice while also suppressing local inflammation by sequestering inflammatory factors.
Given that inflammation and ROS overproduction are hallmarks of atherosclerosis, Gao and colleagues hypothesized that this novel drug delivery system might provide high targeting efficiency and therapeutic efficacy. The macrophage membrane would enable the nanoparticles to evade clearance by the reticuloendothelial system and would target delivery to inflammatory sites, and the ROS responsiveness would enable specific drug release owing to the high local levels of ROS.
The researchers generated nanoparticles with a compound that degrades in the presence of H2O2 (thereby releasing the payload), loaded them with atorvastatin and coated them with cell membrane derived from mouse macrophages. The loaded biomimetic nanoparticles reduced inflammation and foam cell formation in vitro. These anti-inflammatory effects were mediated by atorvastatin and by receptors present on the macrophage membrane, which bound and sequestered pro-inflammatory cytokines and chemokines. In a mouse model of atherosclerosis, the loaded biomimetic nanoparticles had high targeting efficiency and showed targeted drug release to atherosclerotic plaques, leading to reduced plaque inflammation and decreased plaque burden. The cell-membrane system had better therapeutic efficacy than a live-cell carrier consisting of ROS-responsive nanoparticles internalized in macrophages, even though the live-cell system had a higher accumulation rate in the plaques.
Given that this macrophage-biomimetic delivery system has inflammation tropism without the need for specific targeting molecules, this strategy might hold promise for other inflammatory diseases.
Gao, C. et al. Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines. Nat. Commun. 11, 2622 (2020)
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Fernández-Ruiz, I. Macrophage mimetics to target atherosclerosis. Nat Rev Cardiol 17, 454 (2020). https://doi.org/10.1038/s41569-020-0404-x
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