An Oxazine‐Based Fluorogenic Probe with Changeable π‐Conjugation to Eliminate False‐Positive Interference of Albumin and Its Application to Sensing Aminopeptidase N

Abstract

Many fluorophores/probes suffer from the interference of albumin in biosystems. Herein, we propose an effective strategy to overcome this interference by virtue of both an albumin‐insensitive fluorophore and its changeable π‐conjugation, and demonstrate the strategy by designing an oxazine‐based fluorogenic probe for aminopeptidase N (APN). The modification on the N atom in the oxazine fluorophore with alanine through a cleavable linker locks the resulting probe in a non‐conjugated, colorless and non‐fluorescent state, so the non‐specific interaction of albumin produces no spectroscopic response. APN can selectively cleave the alanine moiety, restoring the large π‐conjugation and strong fluorescence. The capability of the probe to eliminate the albumin influence has been demonstrated by imaging APN in different cell lines, and by quantitatively determining APN in human serum and mouse urine. The present strategy may be useful for developing more specific fluorogenic probes for other enzymes.

Combination of changeable π-conjugation and hydrophilic groups for developing water-soluble small-molecule NIR-II fluorogenic probes

“…Since the conjugation transformation of the probe is dominantly regulated by the analyte of interest, CCS probes usually display higher selectivity and sensitivity. 33 Unfortunately, such off–on probes in the NIR-II region are rare. Worse still, most of the existing NIR-II fluorophores or probes suffer from poor water solubility, and a high fraction (>10%, v/v) of organic solvents has to be used, which may inevitably cause severe damage to living organisms or give results deviating from real aqueous bio-environments.…”

Membrane-tethered activation design of a photosensitizer boosts systemic antitumor immunityviapyroptosis

“…Moreover, the uorescence of aPYCI4 was dramatically decreased for APN pretreated with a specic APN inhibitor bestatin. 24 This result conrmed the specic activation of aPYCI4 by APN.…”

An activatable NIR‐II fluorescent probe for tracking heavy‐metal ion and high‐level salt‐induced oxidative stress in plant sprouts

“…Whereas biomarkeractivatable probes only generate fluorescent signals when they come across the specific biomarker, that's why imaging with biomarker-activatable probes can achieve much higher sensitivity with inappreciable background noise. [44][45][46][47][48][49][50][51][52][53] Therefore, a biomarker-activatable probe with NIR-II fluorescent imaging would provide a utilitarian means for accurate detection of H 2 O 2 in-vivo in the plant sprouts and the ensuing warning of heavy-metal ion or high-level salt pollution in soil/water.…”