During the past decade, there was a fast development of cell-based biomimetic systems, which are commonly derived from cell membranes, cell vesicles, or living cells. Such systems have unique and inherent bioinspired features originating from their parent biological systems. In particular, they are capable of (i) prolonging blood circulation time, (ii) avoiding immune response, (iii) targeting desired sites, (iv) providing antigens in cancer immunotherapy, and (v) loading and delivering therapeutic or imaging agents. Thus, these biomimetic systems are promising as prevention, detection, diagnosis, and therapeutic modalities. Though promising, these cell-based biomimetic systems are still far from wide application. One of the important reasons is the inevitable difficulty in their further efficient and precise functionalization. Bioorthogonal chemistry results in fast, specific, and high-yielding ligation under mild biological conditions without interactions with surrounding biomolecules or disturbance of the whole biosystem. Moreover, bioorthogonal chemical groups can be introduced into cells, especially into cell membranes, through cellular biosynthesis and metabolic incorporation. Hence, a specific and reliable approach for cell membrane functionalization based on bioorthogonal chemistry has been opportunely put forward and rapidly developed. In this Account, we summarize our recent research on the development of biomimetic systems by integrating bioorthogonal chemistry with biomimetic approaches. First, an exogenously supplied unnatural biosynthetic precursor (e.g., an amino acid or lipid) bearing a bioorthogonal group (e.g., azide or tetrazine) is fed to living cells and metabolically incorporated into targeted biomolecules via cellular biosynthesis regardless of the cell phenotype. After that, different functional molecules can be anchored to the cell membranes through bioorthogonal chemical reactions by using previously inserted "artificial chemical groups". Therefore, this safe, direct, and long-term engineering strategy endows the natural cell-based biomimetic systems with additional chemical or biological performances such as labeling, targeting, imaging, and therapeutic capabilities, providing a powerful tool for the construction of biomimetic systems. Interestingly, we have successfully fabricated various biomimetic systems and applied them in (1) living virus labeling, (2) targeting delivery and enrichment of drugs/imaging agents, and (3) disease theranostics. This Account may contribute to the further development of biomimetic systems and facilitate their biological and biomedical applications in the future. With this Account we also hope to attract more cooperative interests from different fields such as chemistry, materials science, biology, pharmacy, and medicine in promoting lab-to-clinic translation of cell-based biomimetic systems combined with these two cutting-edge techniques.

中文翻译：

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具有生物正交功能的基于细胞膜的仿生系统。

在过去的十年中，基于细胞的仿生系统得到了快速发展，该系统通常源自细胞膜，细胞囊泡或活细胞。此类系统具有源自其父系生物系统的独特且内在的生物启发特征。特别地，它们能够（i）延长血液循环时间，（ii）避免免疫应答，（iii）靶向所需部位，（iv）在癌症免疫疗法中提供抗原，以及（v）加载和递送治疗剂或成像剂。因此，这些仿生系统有望作为预防，检测，诊断和治疗手段。这些有前途的基于细胞的仿生系统尽管还没有广泛应用。重要原因之一是它们进一步有效和精确的功能化不可避免的困难。生物正交化学导致在温和的生物学条件下快速，特异性和高产量的连接，而不会与周围的生物分子发生相互作用或对整个生物系统造成干扰。此外，可以通过细胞生物合成和代谢掺入将生物正交化学基团引入细胞，特别是细胞膜中。因此，已经提出并快速发展了基于生物正交化学的用于细胞膜功能化的特定且可靠的方法。在此报告中，我们通过将生物正交化学与仿生方法相结合，总结了对仿生系统开发的最新研究。首先，外源供应的带有生物正交基团（例如，叠氮化物或四嗪）送入活细胞，并通过细胞生物合成代谢结合到目标生物分子中，而与细胞表型无关。之后，可以使用先前插入的“人工化学基团”通过生物正交化学反应将不同的功能分子锚定到细胞膜上。因此，这种安全，直接和长期的工程策略使基于天然细胞的仿生系统具有其他化学或生物学性能，例如标记，靶向，成像和治疗能力，为仿生系统的构建提供了强大的工具。有趣的是，我们已经成功地制造了各种仿生系统，并将其应用于（1）活病毒标记，（2）靶向药物/显像剂的传递和富集，（3）疾病诊断学。该帐户可能有助于仿生系统的进一步发展，并在将来促进其生物和生物医学应用。通过此帐户，我们还希望吸引来自化学，材料科学，生物学，药学和医学等不同领域的更多合作兴趣，以促进结合这两种尖端技术的基于细胞的仿生系统的实验室到临床的翻译。