Hypochlorous
acid (HOCl) has received special attention by virtue
of its pivotal antimicrobial nature, and the appropriate amount of
HOCl is beneficial to innate immunity of host to cope with microbial
invasion. However, the uncontrollable accumulation of HOCl is implicated
in many human diseases and even cancers. Thus, to determine its deeper
biological functions, it is significantly important to specifically
monitor intracellular HOCl in biosystems. Herein, we rationally designed
a simple fluorescent probe FH-HA on the
basis of the formylhydrazine recognition receptor and rhodamine B
fluorophore. It is worth noting that the formylhydrazine moiety for
the first time is adopted as the recognition receptor for specifically
recognizing HOCl. Additionally, probe FH-HA also exhibited excellent performance in many areas including satisfactory
water-solubility, high specificity, and excellent sensitivity. Notably,
probe FH-HA could quickly respond to HOCl
(within 3 s), which facilitates the tracing of transient HOCl. More
importantly, probe FH-HA was capable of
specifically tracing the fluctuations of endogenous HOCl in living
cells and zebrafish, and it could monitor basal HOCl in cancer cells
to distinguish cancer cells from normal ones.
As a eukaryotic organelle,
the Golgi apparatus plays an essential
role in various physiological activities such as stress response.
The Golgi stress response is an important physiological process of
conferring cytoprotection by regulating the synthesis and metabolism
of bioactive molecules. Therefore, the development of new suitable
in situ analytical techniques for monitoring related small molecular
substances in the stress reaction of the Golgi apparatus is very helpful
for further study of the regulatory mechanism of the Golgi apparatus.
Recent studies have shown that endogenous hydrogen sulfide (H2S) also possesses crucial bioregulatory and protective performances
in the stress response. Therefore, the high-fidelity in situ mapping
of H2S production under the Golgi stress response plays
an important role not only in revealing cytoprotection functions of
H2S in the stress response but also in further understanding
the regulatory mechanism of the Golgi stress response. In this work,
we designed a simple Golgi-targetable H2S fluorescent probe
(Gol-H
2
S) that responds
accurately and sensitively to H2S in the Golgi apparatus
of living cells and zebrafish. On the basis of its superior bioimaging
performances, probe Gol-H
2
S was successfully applied to the in situ visualization of
H2S production under the Golgi stress response elicited
by monensin, a specific-Golgi stressor. The related process of the
Golgi stress response was validated by stimulation and inhibition
experiments. These findings fully demonstrate that H2S
is an alternative biomarker of the Golgi stress response. Moreover,
probe Gol-H
2
S can
also be used as a potential tool for disclosing the detailed H2S-cytoprotection mechanisms under the regulation of the Golgi
stress response in related diseases.
Liver
cancer is a kind of high mortality cancer due to the difficulty
of early diagnosis. And according to the reports, the concentration
of reactive oxygen species (ROS) was higher in cancer cells than normal
cells. Therefore, developing an effective fluorescent probe for hepatoma-selective
imaging of hypochlorous acid (HOCl) which is one of the vital ROS
is of great importance for understanding the role of HOCl in liver
cancer pathogenesis. However, the cell-selective fluorescent probe
still remains a difficult task among current reports. Herein, a galactose-appended
naphthalimide (Gal-NPA) with p-aminophenylether
as a new receptor and galactose moiety as hepatoma targeting unit
was synthesized and employed to detect endogenous HOCl in living HepG2
cells. This probe was proved to possess good water solubility and
could respond specifically to HOCl. In addition, probe Gal-NPA could completely react to HOCl within 3 s meanwhile accompanied
by tremendous fluorescence enhancement. The quantitative linear range
between fluorescence intensities and the HOCl concentrations was 0
to 1 μM (detection limit = 0.46 nM). More importantly, fluorescence
confocal imaging experiments showed that probe Gal-NPA could discriminate hepatoma cells over other cancer cells and simultaneously
trace endogenous HOCl levels in living HepG2 cells. And we thus anticipate
that probe Gal-NPA has the potential application for
revealing the functions of HOCl in hepatoma cells.
Cancer is a serious threat to human health, and there is an urgent need to develop new treatment methods to overcome it. Organelle targeting therapy, as a highly effective and less toxic side effect treatment strategy, has great research significance and development prospects. Being an essential organelle, the Golgi apparatus plays a particularly major role in the growth of cancer cells. Acting as an indispensable and highly expressed antioxidant in cancer cells, glutathione (GSH) also contributes greatly during the Golgi oxidative stress. Therefore, it counts for much to track the changes of GSH concentration in Golgi for monitoring the occurrence and development of tumor cells, and exploring Golgi-targeted therapy is also extremely important for effective treatment of cancer. In this work, we designed and synthesized a simple Golgi-targeting fluorescent probe GT-GSH for accurately detecting GSH. The probe GT-GSH reacting with GSH decomposes toxic substances to Golgi, thereby killing cancer cells. At the same time, the ratiometric fluorescent probe can detect the concentration changes of GSH in Golgi stress with high sensitivity and selectivity in living cells. Therefore, such a GSH-responsive fluorescent probe with a Golgi-targeted therapy effect gives a new method for accurate treatment of cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.