In a creative and unprecedented approach, the team led by Professor Ki-Bum Lee (https://kblee.rutgers.edu/) at Rutgers University has developed a revolutionary therapeutic strategy to address this medical condition. They've developed a type of Chimeric Antigen Receptor Macrophage (CAR-M) equipped with nanoparticle "backpacks." These nano-engineered macrophages are designed to navigate through the disease's microenvironment, identifying and eliminating dead cells—a process known as efferocytosis. This not only halts the buildup of harmful plaque but also potentially reverses the damage caused by atherosclerosis.
Leveraging innovative/developed technology, our team has further developed a novel solution aimed at combating the root cause of cardiovascular disease directly. By ingeniously modifying human monocytes, we've introduced a revolutionary receptor designed to target and absorb CD47-positive apoptotic cells—cells that contribute significantly to the progression of atherosclerosis. What sets our approach apart is the integration of a cyclodextrin lipid nanoparticle, ingeniously attached to the cell membrane. This nanoparticle acts as a powerful agent, scavenging harmful cholesterol crystals, mitigating oxidative stress, and activating anti-inflammatory pathways, thus significantly enhancing the clearance of the problematic cells.
This dual-action technology promises to clear away dead cells and cholesterol deposits and address the underlying mechanisms driving the disease. By doing so, we are not just slowing disease progression; we're targeting its very foundation. As we move forward, our focus will shift towards validating this technology in vivo, offering hope for a transformative treatment strategy in the battle against cardiovascular diseases.
PUBLICATION: S. T. Chuang, J. B. Stein, S. Nevins, C. Kilic Bektas, H. K. Choi, W.-K. Ko, H. Jang, J. Ha, K.-B. Lee, Enhancing CAR Macrophage Efferocytosis Via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling. Adv. Mater. 2024, 2308377. https://doi.org/10.1002/adma.202308377.
AUTHORS: Skylar Chuag, Joshua Stein, Sarah Nevins, Cemile Kilic Bektas, Hye Kyu Choi, Wankyu Ko, Hyunjun Jang, Jihun Ha
CORRESPONDENCE: Prof. Ki-Bum Lee (Rutgers University), https://kblee.rutgers.edu/
KBLEE Group Team: Dr. Jin-Ha Choi, Dr. Hye Kyu Choi, https://kblee.rutgers.edu/
