Abstract 13112: Theranostic Properties of Porphysome Nanoparticles in Atherosclerotic Cardiovascular Disease

Introduction: ‘Porphysome’ nanoparticles contain porphyrin-lipid which permits fluorescent imaging and can be radiolabelled for positron emission tomography (PET) imaging. The outer shell contains the R4F peptide that interacts with scavenger receptor SR-B1, enabling macrophage targeting and therapeutic effects. Aim: To investigate anti-atherosclerotic and imaging properties of porphysomes. Methods: In vitro, porphysome or PBS-treated macrophages were assessed for uptake (fluorescence microscopy), [ 3 H]-cholesterol efflux and inflammatory responses following lipopolysaccharide stimulation (qRT-PCR/ELISA). In vivo, high-fat diet (HFD) fed apolipoprotein ( Apo)e -/- mice were infused for 8 weeks with porphysomes (3x/week, 40mg/kg) or PBS. 64 Cu-porphysomes were detected by fluorescence (IVIS)/PET imaging. Aortas were digested for flow cytometry. Results: In vitro , porphysomes were internalised by macrophages and increased cholesterol efflux (80%, P <0.05), compared to PBS controls. Porphysomes reduced macrophage mRNA levels of inflammatory factors Il-1β (88%), Il-18 (54%) and Ccl5 (75%), and protein secretion of IL-1β (69%) and CCL5 (82%), P <0.05. Porphysomes suppressed inflammasome components Rela (38%), Nlrp3 (69%) and Asc (36%), P <0.05. In Apoe -/- mice, porphysomes were detected in aortic sinus plaque by fluorescence, co-localised with CD68 + macrophages, and by IVIS in aortic arch plaque, with higher fluorescence intensity in HFD (55%) than chow-fed mice. PET imaging found porphysomes localised in hearts. Porphysome uptake was higher in aortic macrophages than endothelial (9-fold) or smooth muscle (4.5-fold) cells ( P <0.05). Porphysome-treated mice had less aortic macrophages (49%) of the M2-like phenotype (60%), than PBS controls. Conclusions: Porphysomes exhibit multi-modal imaging capabilities for identifying plaque and have athero-protective properties, demonstrating theranostic potential for atherosclerosis.