Proton‐Gradient‐Driven Sensitivity Enhancement of Liposome‐Encapsulated Supramolecular Chemosensors

Abstract

An overarching challenge in the development of supramolecular sensor systems is to enhance their sensitivity, which commonly involves the synthesis of refined receptors with increased affinity to the analyte. We show that a dramatic sensitivity increase by 1-2 orders of magnitude can be achieved by encapsulating supramolecular chemosensors inside liposomes and exposing them to a pH gradient across the lipid bilayer membrane. This causes an imbalance of the influx and efflux rates of basic and acidic analytes leading to a significantly increased concentration of the analyte in the liposome interior. The utility of our liposomeenhanced sensors was demonstrated with various hostdye reporter pairs and sensing mechanisms, and we could easily increase the sensitivity towards multiple biologically relevant analytes, including the neurotransmitters serotonin and tryptamine.

A supramolecular cucurbit[8]uril-based rotaxane chemosensor for the optical tryptophan detection in human serum and urine

“…For instance, additional recognition motifs can be installed on the dye and stopper component to enhance the chemosensor’s selectivity. Moreover, the encapsulation of the rotaxane in liposomes or polymersomes 82 , 83 will enhance the binding affinity and selectivity and, at the same time, reduce the remaining impact of interferents present in biofluids. Finally, the immobilization of the rotaxane in polymeric matrices or the development of washable hydrogels should be explored in the future to improve its sensitivity by removing signal artifacts from the autoemission of biofluids.…”

Dual‐Color Real‐Time Chemosensing of a Compartmentalized Reaction Network Involving Enzyme‐Induced Membrane Permeation of Peptides

“…On the other hand, encapsulation inside liposomes has recently been demonstrated to enhance the sensitivity as well as selectivity of chemosensing ensembles. [ 9,26b ]…”

“…[ 8b ] On the other hand, when the reporter pair is placed either in the inside or outside of a compartment (typically a lipid vesicle, to mimic biological membranes or cells) the translocation of an analyte between the compartments can be similarly monitored by a fluorescence change (tandem membrane assay). [ 8c,9 ] We have already used tandem assays in several combinations, for example, to monitor sequential enzymatic reactions (domino tandem assays) [ 10 ] or to monitor the stepwise influx and subsequent efflux of an analyte in tandem membrane assays. [ 8d,e,11 ] However, all previous examples rested on the use of a single reporter pair, which did not allow more than one reaction to be probed simultaneously.…”

Challenges and Opportunities of Functionalized Cucurbiturils for Biomedical Applications

“…11 This technique allowed for monitoring of enzymatic activity, 124 or translocation across lipid bilayer membranes. 125 To expand the scope of biological systems that can be studied by fluorescence using CB [7], several teams grafted different fluorophores on this host. For example, Nau, Hennig, and co-workers developed a host− guest FRET system based on carboxyfluorescein-modified CB [7] (CB [7]-CF, Figure 34) and DAPI for the sensing of DNA (Figure 35), reporting a new method to measure the concentration of DNA.…”

“…Unmodified CB­[7] has regularly been used for biosensing, one of the main methods consisting of displacing a reporter dye from the cavity of the host . This technique allowed for monitoring of enzymatic activity, or translocation across lipid bilayer membranes . To expand the scope of biological systems that can be studied by fluorescence using CB[7], several teams grafted different fluorophores on this host.…”