Challenges and Opportunities of Functionalized Cucurbiturils for Biomedical Applications

Abstract

Cucurbit[n]uril (CB[n]) macrocycles (especially CB [5] to CB [8]) have shown exceptional attributes since their discovery in 2000. Their stability, water solubility, responsiveness to several stimuli, and remarkable binding properties have enabled a growing number of biological applications. Yet, soon after their discovery, the challenge of their functionalization was set. Nevertheless, after more than two decades, a myriad of CB[n] derivatives has been described, many of them used in cells or in vivo for advanced applications. This perspective summarizes key advances of this burgeoning field and points to the next opportunities and remaining challenges to fully express the potential of these fascinating macrocycles in biology and biomedical sciences.

Macrocycle-Based Antibacterial Materials

“…Photodynamic antibacterial agents have attracted considerable attention due to their efficient tissue penetrability, accuracy, noninvasiveness, and controllable features. For instance, CB­[ n ] macrocycles (especially CB[5] to CB[8]) have received increasing attention in various fields due to their stability, water solubility, host–guest complexation, and stimuli-responsiveness, especially in biological applications . We, together with Lee, Wang, and others, constructed antibacterial hybrid nanoparticles (HAMV-NPs) via ternary host–guest complexation between CB[8], methyl viologen nanoparticles (MV-NPs), and hyaluronic acid (HA) .…”

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

“…130 Nowadays CB[ n ]s have taken over the prominent spot of highly promising macrocyclic candidates for biological applications and drug delivery. 98,122,125,131–151 Moreover, CB[ n ] hosts have shown potential as supramolecular antidotes, neutralizing the effects of a poison though the encapsulation of a small toxic molecule. 147,152,153 The so-called chemical reasons for these new trends are the observations that CDs, when compared to CB[ n ]s, show generally lower selectivity and weaker binding affinities 52 ( K a are usually lower than 10 5 M −1 ).…”

Recent Progress in Site-Selective Modification of Peptides and Proteins Using Macrocycles

“…Further mouse experiments showed that combining insulin with CB[7]–PEG and then administering it to mice can lower blood sugar for a longer period, thereby proving that this strategy can effectively improve the half-life and action time of insulin in vivo . It is noteworthy that, while supramolecular PEGylation eliminates the need for complex chemical modifications on proteins, the synthesis of modified CB[7] poses challenges. , Cucurbiturils are known for their chemical inertness; hence, harsh reaction conditions are often necessary for the direct functionalization of CB­[ n ]. However, the isolated yields in such reactions typically struggle to surpass 30% …”