Nankivell Victoria A, Sandeman Lauren, Stretton Liam, Vidanapathirana Achini K, Rajora Maneesha A, Chen Juan, Tieu William, Weng Hanyi, Kockx Maaike, Kritharides Leonard, Psaltis Peter J, Tan Joanne T M, Chen Yung-Chih, Peter Karlheinz, Zheng Gang, Bursill Christina A
Vascular Research Centre, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, 5000, Australia.
Australian Research Council (ARC) Centre of Excellence for Nanoscale BioPhotonics (CNBP), Australia.
Mater Today Bio. 2025 Aug 21;34:102202. doi: 10.1016/j.mtbio.2025.102202. eCollection 2025 Oct.
Porphyrin-lipid nanoparticles (Por-NPs) have unrealized potential for atherosclerosis. Por-NPs incorporate porphyrin-lipid which permits fluorescence imaging and chelates Copper-64 (Cu) for positron emission tomography (PET) imaging. Their outer shell contains a short peptide 'R4F' that enables macrophage targeting and therapeutic effects. Accordingly, this study investigates the simultaneous diagnostic and therapeutic properties of Por-NPs in atherosclerosis.
, Por-NPs were found to be internalized by immortalised bone marrow-derived macrophages (iBMDMs), visualized via fluorescence microscopy and flow cytometry. Por-NPs also increased cholesterol efflux from [H]-cholesterol-loaded iBMDMs, (49 %, < 0.05). Incubation of iBMDMs with Por-NPs reduced mRNA levels of inflammatory mediators (88 %), (54 %) (75 %) and (92 %), and protein secretion of IL-1β (69 %), CCL5 (82 %) and CCL17 (94 %), < 0.05. Por-NPs suppressed inflammasome components (69 %) and (36 %), < 0.05. Studies using siRNA deletion of SR-B1 and methyl-β-cyclodextrin, revealed the anti-inflammatory properties of Por-NPs were independent of SR-B1 and cholesterol efflux. However, Por-NPs suppressed activation of inflammatory transcription factor NF-κB (53 %, < 0.05). , in mice, serial non-invasive PET imaging showed Cu-labelled Por-NPs localised in hearts and detected increases in plaque size longitudinally with high-cholesterol diet. Por-NP fluorescence was visualized in aortic sinus plaques, co-localised with CD68 macrophages, and by fluorescence IVIS imaging in aortic arch plaque. In two murine models, Por-NP-treated mice had smaller early-stage (22 %) and unstable plaques (52 %). Por-NP-treated mice had fewer circulating (32 %) and aortic (81 %) monocytes, and lower mRNA levels of aortic arch (26 %) and (27 %), < 0.05.
Por-NPs detect plaques using multiple imaging modalities and exhibit atheroprotective effects, presenting as novel nanoscale theranostics for atherosclerosis.
卟啉 - 脂质纳米颗粒（Por - NPs）在动脉粥样硬化治疗方面具有尚未实现的潜力。Por - NPs包含卟啉 - 脂质，可用于荧光成像，并螯合铜 - 64（Cu）用于正电子发射断层扫描（PET）成像。其外壳含有短肽“R4F”，可实现巨噬细胞靶向和治疗效果。因此，本研究探讨了Por - NPs在动脉粥样硬化中的同时诊断和治疗特性。
发现Por - NPs可被永生化骨髓来源的巨噬细胞（iBMDMs）内化，通过荧光显微镜和流式细胞术可视化。Por - NPs还增加了[H] - 胆固醇负载的iBMDMs的胆固醇流出（49%，P < 0.05）。用Por - NPs孵育iBMDMs可降低炎症介质（88%）、（54%）、（75%）和（92%）的mRNA水平，以及IL - 1β（69%）、CCL5（82%）和CCL17（94%）的蛋白分泌，P < 0.05。Por - NPs抑制炎性小体成分（69%）和（36%），P < 0.05。使用SR - B1的siRNA缺失和甲基 - β - 环糊精的研究表明，Por - NPs的抗炎特性独立于SR - B1和胆固醇流出。然而，Por - NPs抑制炎性转录因子NF - κB的激活（53%，P < 0.05）。在小鼠中，连续无创PET成像显示铜标记的Por - NPs定位于心脏，并通过高胆固醇饮食纵向检测到斑块大小增加。Por - NP荧光在主动脉窦斑块中可见，与CD68巨噬细胞共定位，并通过荧光IVIS成像在主动脉弓斑块中可见。在两种小鼠模型中，经Por - NP处理的小鼠早期斑块（22%）和不稳定斑块（52%）较小。经Por - NP处理的小鼠循环单核细胞（32%）和主动脉单核细胞（81%）较少，主动脉弓（26%）和（27%）的mRNA水平较低，P < 0.05。
Por - NPs使用多种成像方式检测斑块并表现出动脉粥样硬化保护作用，是一种新型的动脉粥样硬化纳米级诊疗方法。
