Cholinesterase-Responsive Supramolecular Vesicle

Abstract

Enzyme-responsive, amphiphilic self-assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites where the target enzyme is located. The supramolecular approach, using "superamphiphiles", provides a smart way to fabricate drug delivery systems responsive to enzymatic catalysis. In this work based on the concept of supramolecular chemistry, we report an enzyme-responsive vesicle using p-sulfonatocalix[4]arene as the macrocyclic host and natural enzyme-cleavable myristoylcholine as the guest molecule. The complexation of p-sulfonatocalix[4]arene with myristoylcholine directs the formation of a supramolecular binary vesicle, which is dissipated by cholinesterase with high specificity and efficiency. Cholinesterase is a key protein overexpressed in Alzheimer's disease, and therefore, the present system may have potential for the delivery of Alzheimer's disease drugs.

Biomedical Applications of Supramolecular Systems Based on Host–Guest Interactions

“…Afterward, they further developed an enzymeresponsive supramolecular vesicle by employing biocompatible p-sulfonatocalix [4]arene (SC4A) to deliver tacrine specifically for the treatment of Alzheimer's disease. 198 The binary vesicle was formed by the host−guest complexation between SC4A and myristoylcholine. The vesicle exhibited highly specific and efficient responsiveness to cholinesterase enzyme that could break the hydrophilic−hydrophobic balance, leading to the disassembly of the binary vesicle and thus the release of loaded drugs.…”

Sequentially Programmable and Cellularly Selective Assembly of Fluorescent Polymerized Vesicles for Monitoring Cell Apoptosis

“…5 U mL −1 butyrylcholinesterase (BChE) was employed according to the average activity of cholinesterase present in human tissues 47, 48. Incubation with BChE for 2 d converted DC to DA,49, 50, 51, 52 and then the DC micelles changed to the DA vesicles. Irradiation at 254 nm for 5 min led to the formation of the blue‐form PDA, and followed by a warming process at 37 °C, the desired fluorescent polymerized vesicles, red‐form PDA, were expectedly constructed, exhibiting red emission over 600 nm (Figure S14, Supporting Information).…”

Enzymatic Biodegradation of Hydrogels for Protein Delivery Targeted to the Small Intestine

“…Polymers that degrade by hydrolysis, such as polyanhydrides 25,26 , poly(orthoesters) 2,27 , poly(caprolactone), and poly(lactic acid) and poly(glycolic acid) 28,29 are widely used for drug delivery. However, polymers that undergo enzyme-catalyzed degradation 4 are becoming attractive as site-specific delivery vehicles due to the localized concentration of enzymes throughout the body as well as the specificity of enzymatic attack 30,31 . A relatively small number of researchers have investigated the use of hydrogels with enzyme-degradable peptide components for the purpose of drug delivery to the small intestine 30,32,33 , where enzymes such as trypsin, chymotrypsin, and cathepsin-β are prevalent 34 .…”