A fluorescent, chirality-responsive, and water-soluble cage as a multifunctional molecular container for drug delivery.

In recent years, the rational design and construction of drug delivery systems (DDSs) via a supramolecular approach for improving chemical therapeutics have gained significant attention. Here, we report a host-guest DDS formed from a fluorescent, chirality-responsive, and water-soluble tetraphenylethene-based octacationic cage as a fluorescent/chiral probe, solubilizer, and molecular cargo, which can recognize chiral nucleoside drugs, enhance the solubility of insoluble drugs, and protect drugs from the outside environment by forming host-guest complexes in aqueous solution. Given the fluorescence properties and dynamically rotational conformation of tetraphenylethene (TPE) units, this fluorescent and chirality-responsive cage exhibits different responses including turn-on/turn-off fluorescence and negative/positive circular dichroism (CD) when binding with different chiral nucleoside drugs in water, resulting in multiple-responsive photophysical behaviors for these chiral drugs. Furthermore, this water-soluble cationic cage with a hydrophobic cavity can improve the water solubility of insoluble drugs ( e.g. , CPT) by forming host-guest complexes in water. More importantly, this multifunctional cage exhibits a low toxicity to both human colon and breast cancer cell lines in vitro , and drugs encapsulated by the cage are more effective in killing cancer cells than drugs alone. Finally, the on-off-on fluorescence responses in the formation and dissociation processes of the cage⊃drug complexes have been successfully used to monitor drug release and track drug delivery by fluorescence microscopy in vitro . Therefore, this fluorescent, chirality-responsive, and water-soluble cage as a multifunctional molecular container can be used to construct a smart drug delivery system with several functions of fluorescence and CD detection, water solubilization, real-time monitoring, and chemotherapy.