Nanolipoblockers: Ex Vivo Human Plaque Interaction for Therapeutic Management for Atherosclerosis

Atherosclerosis (AthSc) is escalated by the excessive accumulation of oxidized low density lipoprotein (OxLDL). A new class of nanopolymers, termed nanolipoblockers (NLB), has previously demonstrated inhibition of OxLDL uptake by macrophages. Using an ex vivo human carotid plaque model for targeted intervention with NLB offers potential new mechanisms of AthSc treatment. Carotid plaques were sectioned and incubated in culture medium at 37°C. Samples were treated with the NLBs of different polymer chemistries and 5 μg/mL oxLDL to evaluate NLB binding to plaque and to assess inhibition of plaque recruitment of OxLDL and effect on inflammation. Samples were digested, homogenized, filtered, and fluorescence quantified by flow cytometry and confocal microscopy to identify plaque composition, NLB, and oxLDL uptake. Plaque cells were identified in the specimen showing high levels of NLB binding, merely within 5 minutes, with an increase in uptake in a chemistry-dependent manner after 24 hours (Fig 1). NLBs lowered inflammatory markers in the presence of oxLDL. Furthermore, NLBs caused a marked decrease in the uptake of OxLDL in plaque (Fig 2). AthSc plaques could be targeted through NLB intervention via a reduction in inflammatory substrates and multicellular OxLDL uptake inhibition. This ex vivo model and the NLBs provide a promising therapeutic strategy for the management of active AthSc.