Dorst Daphne N, Boss Marti, Rijpkema Mark, Walgreen Birgitte, Helsen Monique M A, Bos Desirée L, van Bloois Louis, Storm Gerrit, Brom Maarten, Laverman Peter, van der Kraan Peter M, Buitinga Mijke, Koenders Marije I, Gotthardt Martin
Department of Medical Imaging, Radboudumc, Radboud University, 6525 XZ Nijmegen, The Netherlands.
Department of Experimental Rheumatology, Radboudumc, Radboud University, 6525 XZ Nijmegen, The Netherlands.
Pharmaceutics. 2021 Nov 5;13(11):1868. doi: 10.3390/pharmaceutics13111868.
Macrophages play a crucial role in the initiation and progression of rheumatoid arthritis (RA). Liposomes can be used to deliver therapeutics to macrophages by exploiting their phagocytic ability. However, since macrophages serve as the immune system's first responders, it is inadvisable to systemically deplete these cells. By loading the liposomes with the photosensitizer IRDye700DX, we have developed and tested a novel way to perform photodynamic therapy (PDT) on macrophages in inflamed joints. PEGylated liposomes were created using the film method and post-inserted with micelles containing IRDye700DX. For radiolabeling, a chelator was also incorporated. RAW 264.7 cells were incubated with liposomes with or without IRDye700DX and exposed to 689 nm light. Viability was determined using CellTiterGlo. Subsequently, biodistribution and PDT studies were performed on mice with collagen-induced arthritis (CIA). PDT using IRDye700DX-loaded liposomes efficiently induced cell death in vitro, whilst no cell death was observed using the control liposomes. Biodistribution of the two compounds in CIA mice was comparable with excellent correlation of the uptake with macroscopic and microscopic arthritis scores. Treatment with 700DX-loaded liposomes significantly delayed arthritis development. Here we have shown the proof-of-principle of performing PDT in arthritic joints using IRDye700DX-loaded liposomes, allowing locoregional treatment of arthritis.
巨噬细胞在类风湿性关节炎（RA）的起始和进展中起着关键作用。脂质体可利用巨噬细胞的吞噬能力将治疗药物递送至这些细胞。然而，由于巨噬细胞是免疫系统的第一反应者，全身性消耗这些细胞是不可取的。通过将光敏剂IRDye700DX载入脂质体，我们开发并测试了一种对炎症关节中的巨噬细胞进行光动力疗法（PDT）的新方法。采用薄膜法制备聚乙二醇化脂质体，并将含有IRDye700DX的胶束后插入其中。为进行放射性标记，还引入了一种螯合剂。将RAW 264.7细胞与含或不含IRDye700DX的脂质体孵育，并暴露于689 nm光下。使用CellTiterGlo测定细胞活力。随后，对胶原诱导性关节炎（CIA）小鼠进行生物分布和PDT研究。使用载有IRDye700DX的脂质体进行PDT在体外有效诱导细胞死亡，而使用对照脂质体未观察到细胞死亡。两种化合物在CIA小鼠中的生物分布具有可比性，摄取与宏观和微观关节炎评分具有良好的相关性。用载有700DX的脂质体治疗显著延缓了关节炎的发展。在此，我们展示了使用载有IRDye700DX的脂质体在关节炎关节中进行PDT的原理证明，实现了关节炎的局部治疗。
