The porous nature and structural variability of covalent organic frameworks (COFs) make them preferred for drug loading and delivery applications. However, most COF materials suffer from poor luminescent properties and inefficiency for cell uptake. Herein, we experimentally demonstrate the crucial role of long alkoxy chains in the synthesis of crystalline COF nanostructures with high cellular uptake efficiency. After luminescence integration through band engineering, the semiconducting COF exhibits an optical bandgap of 2.05 eV, an emission wavelength of 632 nm, a high quantum yield of 37 %, and excellent fluorescence stability (100 % at 3 h). Such excellent optical properties of the designed COF nanocarriers enable quantitative evaluations of cellular uptake and visual tracking of drug delivery. It was demonstrated that the cellular uptake efficiency was enhanced by orders of magnitude higher for the COF after the introduction of long n-octyloxy chains, which firstly delivered the anticancer camptothecin (CPT) to cell lysosomes, and then underwent “endo/lysosomal escape” to induce cell apoptosis. In vivo assay evidenced a significant enhancement in the therapeutic effect with a 96 % inhibition of tumor growth after 14 days of treatment. This progress sheds light on designing cutting-edge drug delivery nanosystems based on COF materials with integrated diagnostic and therapeutic functions.

中文翻译：

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磷脂激发的烷氧基化诱导发光 COF 纳米载体的结晶和细胞摄取

共价有机框架 (COF) 的多孔性质和结构可变性使其成为药物装载和递送应用的首选。然而，大多数COF材料都存在发光性能差和细胞摄取效率低的问题。在此，我们通过实验证明了长烷氧基链在合成具有高细胞吸收效率的结晶COF纳米结构中的关键作用。通过能带工程进行发光集成后，半导体COF表现出2.05 eV的光学带隙、632 nm的发射波长、37%的高量子产率和优异的荧光稳定性（3小时100%）。设计的 COF 纳米载体具有如此优异的光学特性，可以定量评估细胞摄取和药物输送的视觉跟踪。结果表明，引入长正辛氧基链后，COF的细胞摄取效率提高了几个数量级，首先将抗癌喜树碱（CPT）递送至细胞溶酶体，然后进行“内/溶酶体逃逸”从而诱导细胞凋亡。体内试验证明治疗效果显着增强，治疗 14 天后肿瘤生长抑制率达 96%。这一进展为基于 COF 材料设计具有集成诊断和治疗功能的尖端药物输送纳米系统提供了线索。