Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China.
ACS Nano. 2024 Mar 26;18(12):9176-9186. doi: 10.1021/acsnano.4c01180. Epub 2024 Mar 18.
Immunotherapy plays a vital role in cancer postoperative treatment. Strategies to increase the variety of immune cells and their sustainable supply are essential to improve the therapeutic effect of immune cell-based immunotherapy. Here, inspired by tertiary lymphoid structures (TLSs), we present a microfluidic-assisted microporous annealed particle (MAP) scaffold for the persistent recruitment of diverse immune cells for cancer postoperative therapy. Based on the thermochemical responsivity of gelatin methacryloyl (GelMA), the MAP scaffold was fabricated by physical cross-linking and sequential photo-cross-linking of GelMA droplets, which were prepared by microfluidic electrospraying. Due to the encapsulation of liquid nitrogen-inactivated tumor cells and immunostimulant, the generated MAP scaffold could recruit a large number of immune cells, involving T cells, macrophages, dendritic cells, B cells, and natural killer cells, thereby forming the biomimetic TLSs . In addition, by combination of immune checkpoint inhibitors, a synergistic anticancer immune response was provoked to inhibit tumor recurrence and metastasis. These properties make the proposed MAP scaffold-based artificial TLSs of great value for efficient cancer postoperative therapy.
免疫疗法在癌症术后治疗中起着至关重要的作用。增加免疫细胞的种类和可持续供应的策略对于提高基于免疫细胞的免疫疗法的治疗效果至关重要。在这里，受三级淋巴结构（TLS）的启发，我们提出了一种微流控辅助的微孔退火颗粒（MAP）支架，用于持续招募多种免疫细胞进行癌症术后治疗。基于明胶甲基丙烯酰（GelMA）的热化学响应性，通过微流控电喷雾制备 GelMA 液滴，通过物理交联和顺序光交联制备 MAP 支架。由于封装了液氮灭活的肿瘤细胞和免疫刺激剂，所生成的 MAP 支架可以募集大量的免疫细胞，包括 T 细胞、巨噬细胞、树突状细胞、B 细胞和自然杀伤细胞，从而形成仿生 TLSs。此外，通过联合免疫检查点抑制剂，引发协同的抗癌免疫反应，以抑制肿瘤复发和转移。这些特性使得基于所提出的 MAP 支架的人工 TLSs 在高效癌症术后治疗方面具有重要价值。
