Rahikkala Antti, Fontana Flavia, Bauleth-Ramos Tomás, Correia Alexandra, Kemell Marianna, Seitsonen Jani, Mäkilä Ermei, Sarmento Bruno, Salonen Jarno, Ruokolainen Janne, Hirvonen Jouni, Santos Hélder A
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki FI-00014 Helsinki Finland
Instituto de Investigação e Inovação em Saúde (I3S), University of Porto Rua Alfredo Allen, 208 4200-135 Porto Portugal.
RSC Adv. 2020 Sep 23;10(58):35198-35205. doi: 10.1039/d0ra05900e. eCollection 2020 Sep 21.
Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, long circulation time, and capability to transport cargo all around the body, thus presenting enormous potential in medical applications. In this study, we investigated hybrid nanoparticles consisting of nano-sized autologous or allogeneic red blood cell (RBC) membranes encapsulating porous silicon nanoparticles (PSi NPs). These NPs were functionalized with a model cancer antigen TRP2, which was either expressed on the surface of the RBCs by a cell membrane-mimicking copolymer polydimethylsiloxane--poly-2-methyl-2-oxazoline, or attached on the PSi NPs, thus hidden within the encapsulation. When in the presence of peripheral blood immune cells, these NPs resulted in apoptotic cell death of T cells, where the NPs having TRP2 within the encapsulation led to a stronger T cell deletion. The deletion of the T cells did not change the relative proportion of CD4 and cytotoxic CD8 T cells. Overall, this work shows the combination of nano-sized RBCs, PSi, and antigenic peptides may have use in the treatment of autoimmune diseases.
基于红细胞的药物递送系统因其生物相容性、长循环时间以及在全身运输货物的能力而受到研究，因此在医学应用中展现出巨大潜力。在本研究中，我们研究了由包裹多孔硅纳米颗粒（PSi NPs）的纳米级自体或异体红细胞（RBC）膜组成的杂化纳米颗粒。这些纳米颗粒用模型癌抗原TRP2进行功能化，TRP2要么通过细胞膜模拟共聚物聚二甲基硅氧烷 - 聚 - 2 - 甲基 - 2 - 恶唑啉在红细胞表面表达，要么附着在PSi NPs上，从而隐藏在封装内部。当在外周血免疫细胞存在的情况下，这些纳米颗粒导致T细胞凋亡性死亡，其中封装内含有TRP2的纳米颗粒导致更强的T细胞缺失。T细胞的缺失并未改变CD4和细胞毒性CD8 T细胞的相对比例。总体而言，这项工作表明纳米级红细胞、PSi和抗原肽的组合可能在自身免疫性疾病的治疗中具有应用价值。
