Supramolecular complexation with kinetic stabilization: cucurbit[6]uril encapsulated doxorubicin-based prodrugs for pH-responsive controlled release?

New Journal of Chemistry Pub Date: 2022-02-18 DOI: 10.1039/D1NJ06237A

Abstract

Supramolecular complexation of cucurbit[6]uril and doxorubicin-based guests with slow dissociation was developed for pH-responsive controlled release. The dissociation half-life of the supramolecular complex was up to 31.8 h under physiological conditions, which rendered the complex kinetically stable for up to 10.0 h in blood serum. Supramolecular complexation significantly influenced the serum protein binding and acid-triggered degradation of doxorubicin-based guests. Cell uptake assays indicated that the internalization of doxorubicin was improved at the tumor extracellular pH of 6.5, compared to that at the physiological pH of 7.4. Cytotoxicity assays confirmed that the anticancer efficacy was reduced at neutral pH (7.4), and enhanced at acidic pH (6.5). These results show that the kinetically-stabilized supramolecular complexes may be used for targeted delivery of doxorubicin to tumor tissues, which could help avoid severe side effects toward normal tissues.

Graphical abstract: Supramolecular complexation with kinetic stabilization: cucurbit[6]uril encapsulated doxorubicin-based prodrugs for pH-responsive controlled release
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