Due to its simplicity, high efficiency, and chemo-selectivity, bioorthogonal chemistry has shown a great application potential in pre-targeting. Currently, four bioorthogonal pairs as targeting tools, including (strept)avidin/biotin, antibody/antigen, oligonucleotide hybridization and IEDDA tools, have been developed and applied in targeted delivery. Nevertheless, all of these tools still suffer from some limitations, such as difficult modification, biochemical fragility and larger molecular weight for biological association tools, as well as chemical instability for IEDDA tools. Synthetic host-guest pairs with relatively small molecular sizes not only possess strong chemical stability, but also have the features of fast conjugation rate, tunable binding affinity, easy modification, and high chemo-selectivity. Consequently, they can be used as a novel non-covalent bioorthogonal tool for pre-targeting. In order to further promote the development of host-guest pairs as novel bioorthogonal tools for pre-targeted delivery, we firstly calculate their conversion rate to make researcher aware of their unique advantages; next, we summarize the recent research progress in this area. The future perspectives and limitations of these unique tools will be discussed. This review will provide a systemic overview of the development of synthetic host-guest pairs as novel bioorthogonal tools for pre-targeting, and may serve as a “go for” resort for researchers who are interested in searching for new synthetic tools to improve pre-targeting.

由于其简单、高效和化学选择性，生物正交化学在预靶向方面显示出巨大的应用潜力。目前，已开发出四种生物正交对作为靶向工具，包括（链霉）亲和素/生物素、抗体/抗原、寡核苷酸杂交和IEDDA工具，并应用于靶向递送。然而，所有这些工具仍然受到一些限制，例如生物关联工具的难以修改、生化脆弱和较大的分子量，以及IEDDA工具的化学不稳定性。合成的分子尺寸相对较小的主客体对不仅具有较强的化学稳定性，而且具有结合速率快、结合亲和力可调、易于修饰和化学选择性高等特点。因此，它们可以用作预靶向的新型非共价生物正交工具。为了进一步促进主客体对作为预靶向递送的新型生物正交工具的发展，我们首先计算其转化率，以使研究人员意识到其独特的优势；接下来，我们总结一下该领域的最新研究进展。我们将讨论这些独特工具的未来前景和局限性。这篇综述将系统地概述合成主客体对作为用于预靶向的新型生物正交工具的发展，并且可以作为有兴趣寻找新的合成工具来改善预靶向的研究人员的“选择”手段。瞄准。