本文要点：
尽管面临成本高昂和制造复杂的挑战，工程免疫细胞疗法已被证明是一种革命性的癌症治疗方法。
在这项研究中，作者提出了一个简洁的“脂滴融合”策略的工程巨噬细胞。由于疏水烷基链和π共轭结构的整合，温和合成的sp2C共轭共价有机框架(COF) UM-101诱导巨噬细胞的脂滴融合和代谢重编程，从而促进其抗肿瘤经典活化。
静脉注射UM-101工程巨噬细胞有效地抑制了肿瘤的发展。这些结果代表了用于工程化免疫细胞治疗的sp2C缀合的COFs的室温合成的首次报道，为通过细胞器操作开发治疗性免疫细胞提供了新的视角。
Figure 1. Ambient synthesis of sp2C-conjugated COFs for engineered macrophage therapy. a) Synthetic schemes. Synthetic conditions: (i) acetonitrile/isopropanol (5:1, v/v), KOH (4 M), 25°C, 12 h; (ii) acetonitrile/methyl acetate (2:1, v/v), KOH (4 M), 25°C, 72 h; (iii) acetonitrile, acetic acid, 25°C, 12 h. b) Schematic of macrophage engineering and immunotherapy (created using BioRender.com).
Figure 2. COF characterization. a–c) Stacking models of the proposed structures. d–f) PXRD analysis, showing the experimental patterns (black), Pawley-refined patterns (red), simulated patterns (blue), difference plots (green), and Bragg positions (brown). g–i) N2 adsorption–desorption isotherms at 77 K. Inset: pore size distribution profiles. j–l) 13C ssNMR spectra. m–o) SEM and TEM images.
Figure 3.Surface chemical properties of COFs and COF-induced LD fusion. a) Contact angles of COF powders at the water–air interface. b) Zeta potentials of COF nanoparticles. c) Confocal laser scanning microscopy images of BODIPY 493/503-staining LDs inside macrophages treated with UM-101, UM-102, and UM-103 (50 µg/mL, 24 h). Data are expressed as mean ± SD, n = 3 (a) or 4 (b).
Figure 4. Classical activation and enhanced phagocytosis of macrophages induced by UM-101, UM-102, and UM-103 (50 µg/mL, 24 h)
Figure 5. COF-activated macrophages for engineered immune cell therapy of colon tumor-bearing BALB/c mice
https://doi.org/10.1002/anie.202421416
