Design and Construction of a Smart Targeting Drug Delivery System Based on Phototriggered Competition of Host–Guest Interaction

A smart targeting drug delivery nanocarrier is successfully constructed based on phototriggered competition of host–guest interaction. The targeting motif, i.e., biotin is first concealed by β‐cyclodextrin (β‐CD) via host–guest interaction. When the nanoparticles are exposed to UV light, the cleavage of photosensitive groups results in the exposure of adamantane (Ad) groups initially located in the interior of nanoassemblies, and β‐CDs capped on biotin ligands can be replaced by Ad because of the higher binding constant between Ad and β‐CD than that between biotin and β‐CD. The competition of host–guest interaction leads to the recovery of targeting capacity of biotin ligands on the nanocarriers. By virtue of photoregulation, the nanocarriers exhibit controllable ligand‐receptor recognition, which is proved by flow cytometry, laser confocal microscopy, and cytotoxicity assay. This strategy has a potential to improve the selectivity and safety of targeting drug delivery systems.