Supramolecular Chemotherapy with Cucurbit[n]urils as Encapsulating Hosts

Abstract

The cucurbit[n]urils (CB[n]) belong to the field of relatively young supramolecules which act as containers for a large variety of guests and are being explored extensively for their numerous biomedical applications. This includes drug formulation and delivery, controlled drug release, photodynamic therapy, sensing for bioanalytical purposes, etc. These supramolecular host–guest systems have distinctive recognition properties and have successfully been shown to enhance the in vitro and in vivo utility of various chemotherapeutic agents. The CB[n]s are tailored to optimize their application in payload delivery and diagnostics and in lowering the toxicity of existing drugs. This review has listed the recent studies on working mechanisms and host–guest complexation of the biologically vital molecules with CB[n] and highlighted their implementation in anticancer therapeutics. Various modifications in CB-drug inclusion compounds like CB supramolecular nanoarchitectures along with application in photodynamic therapy, which has shown potential as targeted drug delivery vehicles in cancer chemotherapy, have also been discussed.

Overcoming barriers with non-covalent interactions: supramolecular recognition of adamantyl cucurbit[n]uril assemblies for medical applications

“…This principle of conditioning cytotoxicity in chemotherapy by applying supramolecular systems was adopted as a new strategy aptly named supramolecular chemotherapy (Fig. 6), [169][170][171] and is an illustrative proof-ofprinciple of integrating non-covalent interactions into a synergy of drug design, targeted delivery and combined drug therapy.…”

“…Additionally, CB[n] macrocycles in the role of host molecules 80 could be implemented with other systems to build heterogeneous nano-assemblies, also with promising potential biological applications like drug and gene delivery, bioimaging, and photodynamic cancer therapy. 131,137,171,[260][261][262][263][264][265][266][267][268][269][270] In such hybrid systems CB[n]s are typically carrier vehicles for biologically active compounds or are functional parts of the emerging nanostructure and are therefore involved in controlling drug release mechanism from the nanomaterial. Up to now cucurbit[n]urils have successfully been combined with other nanomaterials 271 like polymers, [272][273][274][275][276] proteins, [131][132][133] (e.g., bovine serum albumin), metal nanoparticles, [277][278][279][280][281] etc.…”

Evaluation of the Immunosafety of Cucurbit[n]uril In Vivo

“…[ 1 , 2 , 3 ]. Among cavitands, cucurbiturils have advantages, such as the ability to form strong complexes with various compounds [ 4 , 5 , 6 , 7 ]. Cucurbit[n]uril (CB[n], C 6n H 6n N 4n O 2n , n = 5–10), a class of compounds first discovered by Behrend et al in 1905, have recently emerged as promising macrocyclic containers formed by the acid-catalyzed condensation of n glycoluril units with formaldehyde [ 8 ].…”

Tumor Microenvironment ROS/pH Cascade-Responsive Supramolecular Nanoplatform with ROS Regeneration Property for Enhanced Hepatocellular Carcinoma Therapy

“…Recently, supramolecular nanoparticles (NPs) based on host–guest interaction have attracted considerable attention in drug delivery, owing to their surface area, high drug encapsulation effect, reversibility, and switchable structures. , Particularly, the supramolecular architectures benefit in reversibly combining several functional blocks, like targeted ligands and responsive moieties, separately into a single platform, to equip the NPs with multiple functions . Several macrocyclic host molecules, such as cyclodextrins (CDs), pillararenes (or pillar­[ n ]­arenes), and cucurbit­[ n ]­urils, have been used as carriers for drug delivery. Therein, the self-assembled supramolecular NPs composed of the strong host–guest interactions between CDs and adamantine exhibit the unique performance in drug and gene delivery applications − due to the simple synthesis procedure, the spontaneous interaction to generate the shell–core structure, and high drug loading efficiency.…”