In vivo reversal of general anesthesia by cucurbit[7]uril with zebrafish models

Abstract

A general anesthetic is a drug that brings about a reversible loss of consciousness, during a surgical or therapeutic procedure to render the patient free of pain and anxiety. However, the effect of anesthetics may linger far beyond the necessary time required and induce adverse effects. In addition, many surgical patients need to recover to a conscious state that allows them to make important decisions soon after their surgery. Unfortunately, there are currently no clinically-available anti-dotes to reverse the effects of anesthetics. In this study, we demonstrate the in vitro supramolecular host-guest complexations between macrocyclic cucurbit [7]uril (CB [7]) and a commonly used general anesthetic in fish, tricaine mesylate (TM), and we report for the first time the in vivo reversal effect of CB [7] to general anesthesia induced by TM with zebrafish models. These findings might lead to a new approach that may allow patients to regain lucidity much faster than their natural recovery from general anesthesia, and may also be used to reverse potentially life-threatening toxic effects encountered by some patients in response to general anesthesia.

Cucurbit[7]uril Enables Multi-Stimuli-Responsive Release from the Self-Assembled Hydrophobic Phase of a Metal Organic Polyhedron

“…1b,3 In addition, CB[n]-type receptors exhibit good biocompatibility, and have therefore been used to formulate, protect, and deliver drugs, as reversal agents to mitigate drug (side) effects, and for various sensing applications. 4 Earlier, the excellent recognition properties of CB[n] were combined with nanoparticles for biological and material applications. 5 For example, the Zink, Stoddart, and Yang groups have created mesoporous silica nanoparticles that are gated by host-guest recognition processes.…”

Metal–Organic Polyhedron Capped with Cucurbit[8]uril Delivers Doxorubicin to Cancer Cells

“…27,31,32 Given their excellent biocompatibility, other recent efforts have sought to use CB[n]-type receptors to enhance drug solubility, for imaging applications, and as a drug reversal agent. 31,33 Pioneering work in this area was performed by Yang, Zink, and Stoddart based on mesoporous silica nanoparticles that are gated by host•guest recognition processes. 23,34 In this paper, we decorate the external surface of Fujita-type Pd 12 L 24 metal organic polyhedra (MOP) with MV ligands, explore their non-covalent functionalization with CB[n], and demonstrate their ability to deliver doxorubicin to cancer cells.…”

Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor

“…19 Very recently, our group reported the ability of CB [7] to reverse the effects of general anesthesia induced by tricaine in vivo. 11 It has also been shown that the myotoxicity and cardiotoxicity of cisplatin was significantly reduced after this drug had been encapsulated by CB [7]. 20 CB [7] was also found to inhibit amyloid fibrillation, thus potentially finding therapeutic applications to prevent or treat amyloidosis.…”