Stimuli-Responsive Cucurbit[n]uril-Based Supramolecular Nanocarriers for Delivery of Chemotherapeutics

Chemotherapeutics commonly exhibit low bioavailability and systemic adverse effects. Supramolecular nanovesicles, such as pillar[n]arenes, calix[n]arenes, cucurbit[n]urils (CBs), and cyclodextrins, have been introduced as promising nanocarriers due to their remarkable encapsulation capacity and ability to host hydro-philic/-phobic guest molecules. Additionally, such nano vesicles can be decorated with various stimuli-responsive entities to enable drug targeting and controlled drug release. Self-assembly of amphiphilic cavitands and host-guest complexation represent the two common approaches for preparation of supramolecular nanovesicles with customizable surfaces capable of accommodating different biologically active guest molecules. CBs have been used as smart and multifunctional host macromolecules in cancer therapy. CBs are fabricated via a condensation reaction between formaldehyde and glycoluril units generating barrel-shaped supramolecules with partially enclosed cavities. The unique structure of CBs surrounding an internal hydrophobic cavity allows them to accommodate cationic and neutral guest molecules via ion-dipole and hydrophobic interactions, respectively. Additionally, CBs are stable, safe, and biocompatible, and their surfaces can be decorated with various functional targeting moieties. These advantages have promoted CBs as promising candidates for stimuli-responsive targeted delivery of chemotherapeutics. This review presents the most recent advances in the design of stimuli-responsive nanosystems based on CBs for effective cancer treatment.