Current research has demonstrated that mitochondrial morphology, distribution, and function are maintained by the balanced regulation of mitochondrial fission and fusion, and perturbation of the homeostasis between these processes has been related to cell or organ dysfunction and abnormal mitochondrial redistribution. Abnormal mitochondrial fusion induces the fragmentation of mitochondria from a tubular morphology into pieces; in contrast, perturbed mitochondrial fission results in the fusion of adjacent mitochondria. A member of the dynamin family of large GTPases, dynamin-related protein 1 (Drp1), effectively influences cell survival and apoptosis by mediating the mitochondrial fission process in mammals. Drp1-dependent mitochondrial fission is an intricate process regulating both cellular and organ dynamics, including development, apoptosis, acute organ injury, and various diseases. Only after clarification of the regulative mechanisms of this critical protein in vivo and in vitro will it set a milestone for preventing mitochondrial fission related pathological processes and refractory diseases.
Cysteine (Cys), as an important biothiol, plays a major role in many physiological processes like protein synthesis, detoxification and metabolism, and also is closely associated with a variety of diseases; thus the design of novel highly selective and sensitive near-infrared (NIR) fluorescent probes for Cys detection in vivo is of great significance. Herein, we report a selective and sensitive NIR turn-on fluorescent probe (CP-NIR) with large Stokes shift for detecting Cys in vivo. Upon addition of Cys to the solution of the probe, it is absorption wavelength shifts from 550 to 600 nm, accompanying with an obvious enhancement of NIR fluorescence emission centering around 760 nm. This Michael-addition reaction-based probe shows a large Stokes shift (160 nm), low detection limit (48 nM), fast response time, and low toxicity. Moreover, this novel NIR probe with good cell permeability was successfully applied to monitoring endogenous Cys in living cells and in a mouse model.
The ratiometric fluorescence assay, which can eliminate the external effects, has attracted great attention. In this work, a carbon dot (CD)-based nanohybrid dual-emission system was simply prepared by a unique approach of solvothermal treating corn bract and used as a ratiometric fluorescent sensor for Hg detection. Under a single excitation, the obtained nanohybrid sensor had two emission bands around 470 and 678 nm, which may originate from the intrinsic structure of CDs and chlorophyll-derived porphyrins, respectively. In the presence of Hg, the fluorescence at 678 nm could be remarkably quenched, while the fluorescence intensity at 470 nm was only slightly altered. The fluorescence intensity ratio at 470 and 678 nm exhibited a good linear relationship in the Hg concentration range from 0 to 40 μM with a detection limit of about 9.0 nM. It also had a satisfying assay performance in serum and river water samples. The prepared CD-based nanohybrid sensor here may hold the further potential applications in biomedicine study, environmental protection, and food safety.
Tumor microenvironment–responsive therapy has enormous application potential in the diagnosis and treatment of cancer. The glutathione (GSH) level has been shown to be significantly increased in tumor tissues. Thus, GSH can be used as an effective endogenous molecule for diagnosis and tumor microenvironment–activated therapy. In this study, we prepared a tumor microenvironment–induced, absorption spectrum red-shifted, iron-copper co-doped polyaniline nanoparticle (Fe-Cu@PANI). The Cu(II) in this nanoparticle can undergo a redox reaction with GSH in tumors. The redox reaction induces a red shift in the absorption spectrum of the Fe-Cu@PANI nanoparticles from the visible to the near-infrared region accompanying with the etching of this nanoparticle, which simultaneously activates tumor photoacoustic imaging and photothermal therapy, thereby improving the accuracy of in vivo tumor imaging and the efficiency of photothermal therapy. The nanoparticle prepared in this study has broad application prospects in the diagnosis and treatment of cancer.
Drug-induced liver injury (DILI)
is a frequent cause of hepatic
dysfunction as well as the single most frequent reason for removing
approved medications from the market, and multispectral optoacoustic
tomography (MSOT) is an emerging and noninvasive imaging modality
for diagnosing and monitoring diseases. Herein, we report an activatable
optoacoustic probe for imaging DILI through detecting the activity
of leucine aminopeptidase (LAP). In this probe, an N-terminal leucyl
moiety serving as the LAP recognition element is linked with a chromene-benzoindolium
chromophore via 4-aminobenzylalcohol group. The elevated expression
of hepatic LAP as a result of DILI cleaves the leucyl moiety and causes
the red-shift of the probe’s absorption band, thereby generating
prominent optoacoustic signals for MSOT imaging. During this process,
the probe also exhibits prominent NIR fluorescence, which can be utilized
for fluorescent imaging. More importantly, by rendering stacks of
cross-sectional images as maximal intensity projection (MIP) images,
we could precisely locate the focus of drug-induced liver injury in
mice. This probe is expected to serve a powerful tool for studying
physiological and pathological processes related to LAP.
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