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

Abstract

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 nanovesicles 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.

Complexation of Fluorofenidone by Cucurbit[7]uril and β-Cyclodextrin: Keto–Enol Tautomerization to Enhance the Solubility

“…CB­[7] binds to guest molecules based on pH and ionic concentration, and it can regulate the acid–base balance of encapsulated guest molecules. , Furthermore, changing the pH of the environment and the concentration of electrolytes can significantly control the release of the guest molecules in aqueous solutions. , CB[7] tends to bind to cationic molecules due to its carbonyl groups. In this process, CB[7] can promote the protonation of guest molecules, resulting in prototropic tautomerism, in other words, the transfer of proton from one atom to another .…”

Psoralidin–cucurbit[7]uril complex with improved solubility to tackle human colorectal cancer: experimental and computational study

“…Such features have permitted the accommodation of several bioactive compounds inside their cavities, increasing their water solubility, improving their bioavailability, and eventually, escorting the payloads selectively to the intended sites of action. [18][19][20][21][22][23][24][25] Captivatingly, cucurbit[n]urils have shown considerable benefits, such as the facile methods of fabrication, the ability to be decorated with different functional groups, and their potential to form host-guest complexes with various molecules. This presents a promising approach for carrying phytochemicals to the targeted organs while reducing their off-target effects.…”

“…This presents a promising approach for carrying phytochemicals to the targeted organs while reducing their off-target effects. 18,19 To this end, this study utilized cucurbit [7]uril (CB7) to host Ps via host-guest complexation forming Ps@CB7. Several characterization tests have been performed to assess the obtained system features, such as 1 H NMR, UV spectrophotometry, phase solubility study, morphological properties, and dissolution study.…”

“…Such features have permitted the accommodation of several bioactive compounds inside their cavities, increasing their water solubility, improving their bioavailability, and eventually, escorting the payloads selectively to the intended sites of action. 18–25…”

“…This presents a promising approach for carrying phytochemicals to the targeted organs while reducing their off-target effects. 18,19…”