Synthetic host-guest pairs as novel bioorthogonal tools for pre-targeting

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. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

Bioorthogonal chemistry, with its simplicity, high efficiency, and chemo-selectivity, has great potential in pre-targeting applications. Synthetic host-guest pairs, which have small molecular sizes, strong chemical stability, fast conjugation rate, tunable binding affinity, and easy modification, provide a novel non-covalent bioorthogonal tool for pre-targeting. This review provides a comprehensive overview of the development of synthetic host-guest pairs as novel bioorthogonal tools for pre-targeting, serving as a reference for researchers interested in improving pre-targeting.