Fontana Flavia, Molinaro Giuseppina, Moroni Sofia, Pallozzi Giulia, Ferreira Mónica P A, Tello Rubén Pareja, Elbadri Khalil, Torrieri Giulia, Correia Alexandra, Kemell Marianna, Casettari Luca, Celia Christian, Santos Hélder A
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.
Department of Biomolecular Sciences, School of Pharmacy, University of Urbino Carlo Bo, Urbino, I-61029, Italy.
Adv Healthc Mater. 2024 Jun;13(15):e2302074. doi: 10.1002/adhm.202302074. Epub 2024 Mar 24.
Atherosclerosis still represents a major driver of cardiovascular diseases worldwide. Together with accumulation of lipids in the plaque, inflammation is recognized as one of the key players in the formation and development of atherosclerotic plaque. Systemic anti-inflammatory treatments are successful in reducing the disease burden, but are correlated with severe side effects, underlining the need for targeted formulations. In this work, curcumin is chosen as the anti-inflammatory payload model and further loaded in lignin-based nanoparticles (NPs). The NPs are then coated with a tannic acid (TA)- Fe (III) complex and further cloaked with fragments derived from platelet cell membrane, yielding NPs with homogenous size. The two coatings increase the interaction between the NPs and cells, both endothelial and macrophages, in steady state or inflamed status. Furthermore, NPs are cytocompatible toward endothelial, smooth muscle and immune cells, while not inducing immune activation. The anti-inflammatory efficacy is demonstrated in endothelial cells by real-time quantitative polymerase chain reaction and ELISA assay where curcumin-loaded NPs decrease the expression of Nf-κb, TGF-β1, IL-6, and IL-1β in lipopolysaccharide-inflamed cells. Overall, due to the increase in the cell-NP interactions and the anti-inflammatory efficacy, these NPs represent potential candidates for the targeted anti-inflammatory treatment of atherosclerosis.
动脉粥样硬化仍然是全球心血管疾病的主要驱动因素。除了斑块中脂质的积累外，炎症被认为是动脉粥样硬化斑块形成和发展的关键因素之一。全身性抗炎治疗在减轻疾病负担方面取得了成功，但与严重的副作用相关，这突出了对靶向制剂的需求。在这项工作中，选择姜黄素作为抗炎有效载荷模型，并进一步负载到木质素基纳米颗粒（NPs）中。然后用单宁酸（TA）-铁（III）复合物对纳米颗粒进行包覆，并进一步用源自血小板细胞膜的片段进行包裹，得到尺寸均匀的纳米颗粒。这两种涂层增加了纳米颗粒与稳态或炎症状态下的内皮细胞和巨噬细胞之间的相互作用。此外，纳米颗粒对内皮细胞、平滑肌细胞和免疫细胞具有细胞相容性，同时不会诱导免疫激活。通过实时定量聚合酶链反应和酶联免疫吸附测定法在内皮细胞中证明了抗炎效果，其中负载姜黄素的纳米颗粒降低了脂多糖炎症细胞中Nf-κb、TGF-β1、IL-6和IL-1β的表达。总体而言，由于细胞与纳米颗粒相互作用的增加以及抗炎效果，这些纳米颗粒代表了动脉粥样硬化靶向抗炎治疗的潜在候选物。
