Bio-Organic Chemistry, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
ACS Nano. 2022 Sep 27;16(9):15072-15085. doi: 10.1021/acsnano.2c06211. Epub 2022 Aug 15.
Nanosized artificial antigen-presenting cells (aAPCs), synthetic immune cell mimics that aim to activate T cells or , offer an effective alternative to cellular immunotherapies. However, comprehensive studies that delineate the effect of nano-aAPC topology, including nanoparticle morphology and ligand density, are lacking. Here, we systematically studied the topological effects of polymersome-based aAPCs on T cell activation. We employed an aAPC library created from biodegradable poly(ethylene glycol)--poly(d,l-lactide) (PEG-PDLLA) polymersomes with spherical or tubular shape and variable sizes, which were functionalized with αCD3 and αCD28 antibodies at controlled densities. Our results indicate that high ligand density leads to enhancement in T cell activation, which can be further augmented by employing polymersomes with larger size. At low ligand density, the effect of both polymersome shape and size was more pronounced, showing that large elongated polymersomes better activate T cells compared to their spherical or smaller counterparts. This study demonstrates the capacity of polymersomes as aAPCs and highlights the role of topology for their rational design.
纳米级人工抗原呈递细胞（aAPCs）是一种模拟免疫细胞的合成物，旨在激活 T 细胞，为细胞免疫疗法提供了有效的替代方法。然而，目前缺乏全面研究纳米 aAPC 拓扑结构（包括纳米颗粒形态和配体密度）的影响。在这里，我们系统地研究了基于聚合物囊泡的 aAPCs 对 T 细胞激活的拓扑效应。我们使用由可生物降解的聚乙二醇-聚（D，L-丙交酯）（PEG-PDLLA）聚合物囊泡制成的 aAPC 文库，这些囊泡具有球形或管状形状和不同的尺寸，并以可控的密度功能化αCD3 和 αCD28 抗体。我们的结果表明，高配体密度会增强 T 细胞的激活，而使用较大尺寸的聚合物囊泡则可以进一步增强这种效果。在低配体密度下，聚合物囊泡的形状和尺寸的影响更为明显，表明大的长形聚合物囊泡比其球形或较小的对应物更能激活 T 细胞。这项研究展示了聚合物囊泡作为 aAPCs 的潜力，并强调了拓扑结构在其合理设计中的作用。
