Pro-efferocytic nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis

• DOI: 10.1038/s41467-024-52005-1
• Publication Date: 2024-09-13T17:03:54Z
• Authors: Sharika Bamezai; Yapei Zhang; Manisha Kumari; Mozhgan Lotfi; Tom Alsaigh; Lingfeng Luo; Gayatri Suresh Kumar; Fudi Wang; Jianqin Ye; Madhu Puri; Romila Manchanda; Sesha Paluri; Shaunak S. Adkar; Yoko Kojima; Alice Ingelsson; Caitlin F. Bell; Nicolas G. Lopez; Changhao Fu; Ryan B. Choi; Zach Miller; Leo Barrios; Susan Walsh; Ferhaan Ahmad; Lars Maegdefessel; Bryan Ronain Smith; Nicholas J. Leeper
• Keywords: Inflammation; Male; Swine; Science; Macrophages; Q; Anemia; CD47 Antigen; Apoptosis; Atherosclerosis; Article; Plaque, Atherosclerotic; ddc:; Disease Models, Animal; Mice; Phagocytosis; Animals; Nanoparticles; Humans

Atherosclerosis is an inflammatory disorder responsible for cardiovascular disease. Reactivation of efferocytosis, the phagocytic removal cells by macrophages, has emerged as a translational target atherosclerosis. Systemic blockade key 'don't-eat-me' molecule, CD47, triggers engulfment apoptotic vascular tissue and potently reduces plaque burden. However, it also induces red blood cell clearance, leading to anemia. To overcome this, we previously developed macrophage-specific nanotherapy loaded with chemical inhibitor that promotes efferocytosis. Because was found be safe effective in murine studies, aimed advance our nanoparticle into porcine model Here, demonstrate production can scaled without impairing function. At early stage disease, find accumulation inflammation atherosclerotic lesion. Notably, this therapy does not induce anemia, highlighting potential targeted macrophage checkpoint inhibitors.