To accurately monitor the variations of lysosomal nitric oxide (NO) under physiological condition remains a great challenge for understanding the biological function of NO. Herein, we developed a new chemotype probe, namely, MBTD, for acid-promoted and far-red fluorescence imaging of lysosomal NO in vitro and ex vivo. MBTD was rationally designed by incorporating o-phenylenediamino (OPD) moiety into the donor-acceptor-donor (D-A-D) type fluorophore based on a dual intramolecular charge transfer (ICT) mechanism. Compared to previously reported OPD-based NO probes, MBTD displays several distinct advantages including large stroke shift, huge on-off ratio with minimal autofluorescence, and high NO specificity. Particularly, MBTD exhibits an acid-promoted response to NO with high acid tolerance, which greatly improves the spatial resolution to lysosomal NO by excluding the background noise from other nonacidic organelles. Furthermore, MBTD displayed much longer-lived and more stable fluorescence emission in comparison with the commercialized NO probe. MBTD was employed for ratiometric examination of the exogenous or endogenous NO of macrophages. More importantly, MBTD was able to detect the variation of lysosomal NO level in an acute liver injury mouse model ex vivo, implying the potential of MBTD for real-time monitoring the therapeutic efficacy of drug candidates for the treatment of acute liver injury. MBTD as a novel type of NO probe might open a new avenue for precisely sensing lysosomal NO-related pathological and therapeutic process.
Second near‐infrared (NIR‐II) fluorescence imaging with deep tissue‐penetration ability holds remarkable potential for cancer diagnosis. However, clinical translation of NIR‐II fluorescence imaging‐based cancer treatment is severely restricted by the low signal‐to‐background ratio due to insufficient tumor specificity of fluorophores. In this study, it is hypothesized that methylglyoxal (MGO), an intermediate metabolite of tumor glycolysis could be used as a potent biomarker for triggering NIR‐II fluorescence imaging‐guided cancer theranostic. For proof‐of‐concept, first a MGO‐activatable NIR‐II fluorescence probe is developed, and then MGO‐responsive “dual lock‐and‐key” nanotheranostics by integrating the NIR‐II fluorophore and a photodynamic prodrug (i.e., hexyl 5‐aminolevulinic acid hydrochloride (HAL)) into one nanoparticle is engineered. The nanotheranostic can be specifically activated with tumorous MGO for NIR‐II fluorescence imaging‐guided combinatory cancer therapy. Upon 808 nm laser irradiation, the activated NIR‐II fluorophore can generate tunable photothermal effect to trigger HAL release. Subsequently, HAL is converted to protoporphyrin IX inside the tumor cells for 655 nm laser irradiation‐induced photodynamic therapy. It is demonstrated that the NIR‐II fluorescence nanotheranostics is highly specifically activated in the tumor and efficiently suppressed 4T1 breast tumor growth in mouse model. The NIR‐II fluorescence imaging‐based nanotheranostic might imply novel insight into reactive metabolite‐activatable precise therapy of tumor.
In this study, a dual-emission fluorescence resonance energy transfer (FRET) polymeric nanoprobe by single-wavelength excitation was developed for sensitive and selective hydrogen peroxide (HO) detection. Polymeric nanoprobe was prepared by simple self-assembly of functional lipopolymers, which were 4-carboxy-3-fluorophenylboronic acid (FPBA)-modified DSPE-PEG (DSPE-PEG-FPBA) and 7-hydroxycoumarin (HC)-conjugated DSPE-PEG (DSPE-PEG-HC). Subsequent binding of alizarin red S (ARS) to FPBA endowed the nanoprobe with a new fluorescence emission peak at around 600 nm. Because of the perfect match of the fluorescence emission spectra of HC with the absorbance spectra of ARS-FPBA, FRET was achieved between them. The sensing strategy for HO was based on HO-induced deboronation reaction and boronic acid-mediated ARS fluorescence. Interaction between phenylboronic acid and ARS was revisited herein and it was found that electron-donating or -withdrawing group on phenylboronic acid (PBA) has significant influence on the fluorescence property of ARS, which enabled sensitive and selective HO sensing. The nanoprobe displayed two well-separated emission bands (150 nm), providing high specificity and sensitivity for ratiometric detection of HO. Further application was exploited for the determination of glucose and the results demonstrated that the proposed strategy showed ratiometric response capability for glucose detection. The current method does not involve complicated organic synthesis and opens a new avenue for the construction of multifunctional polymeric fluorescent nanoprobe.
The variation of amyloid β peptide (Aβ) concentration and Aβ aggregation are closely associated with the etiology of Alzheimer’s diseases (AD). The interaction of Aβ with the monosialoganglioside-rich neuronal cell membrane has been suggested to influence Aβ aggregation. Therefore, studies on the mechanism of Aβ and sialic acids (SA) interaction would greatly contribute to better understanding the pathogenesis of AD. Herein, we report a novel approach for Aβ–SA interaction analysis and highly sensitive Aβ detection by mimicing the cell surface presentation of SA clusters through engineering of SA-modified peptide nanofiber (SANF). The SANF displayed well-ordered 1D nanostructure with high density of SA on surface. Using FAM-labeled Aβ fragments of Aβ1–16, Aβ16–23, and Aβ24–40, the interaction between Aβ and SA was evaluated by the fluorescence titration experiments. It was found that the order of the SA-binding affinity was Aβ1–16 > Aβ24–40 > Aβ16–23. Importantly, the presence of full-length Aβ1–40 monomer triggered a significant fluorescence enhancement due to the multivalent binding of Aβ1–40 to the nanofiber. This fluorescent turn-on response showed high selectivity and sensitivity for Aβ1–40 detection and the method was further used for Aβ aggregation process monitoring and inhibitor screening. The results suggest the proposed strategy is promising to serve as a tool for mechanism study and the early diagnosis of Alzheimer’s disease.
A near-infrared fluorescent probe for MGO imaging in Alzheimer's disease mouse brains was developed.
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