Mitochondria-Targeted Fluorescent Nanoparticles with Large Stokes Shift for Long-Term BioImaging.

Mitochondria (MITO) play a significant role in various physiological processes and are a key organelle associated with different human diseases including cancer, diabetes mellitus, atherosclerosis, Alzheimer's disease, etc. Thus, detecting the activity of MITO in real time is becoming more and more important. Herein, a novel class of amphiphilic aggregation-induced emission (AIE) active probe fluorescence (AC-QC nanoparticles) based on a quinoxalinone scaffold was developed for imaging MITO. AC-QC nanoparticles possess an excellent ability to monitor MITO in real-time. This probe demonstrated the following advantages: (1) lower cytotoxicity; (2) superior photostability; and (3) good performance in long-term imaging in vitro. Each result of these indicates that self-assembled AC-QC nanoparticles can be used as effective and promising MITO-targeted fluorescent probes.

An aminopeptidase N-based color-convertible fluorescent nano-probe for cancer diagnosis.

Specific cancer diagnosis at an early stage plays a significant role in preventing cancer metastasis and reducing cancer mortality. Thus, exploring specific and sensitive fluorescent probes to realize early cancer diagnosis is an urgent need in clinic. Aminopeptidase N (APN/CD13), overexpressed in numerous malignant tumors, is an important tumor biomarker associated with cancer progression, invasion, and metastasis. In this study, a novel fluorescent molecule APN-SUB, capable of monitoring APN in real time, is encapsulated in a pH-responsive block copolymer (termed APN-SUB nanoprobe) for cancer diagnosis. APN-SUB contains a fluorophore center and a trigger moiety (leucine group), which is covalently conjugated on the fluorophore with an amide bond. The hydrolysis of the amide bond in APN-SUB activated by APN leads to a red shift of maximum fluorescence emission wavelength from 495 nm to 600 nm, realizing dual-color transformation from green to red. Moreover, the APN-SUB nanoprobe with pH-responsiveness is prepared to improve the accumulation and the release rate in the tumor region. It is worth noting that the APN-SUB nanoprobe exhibits good performance for APN imaging, namely, superior limit of detection (0.14 nU mL-1), excellent selectivity and strong photostability. More importantly, the APN-SUB nanoprobe can be successfully employed as a color-convertible fluorescent probe for cancer diagnosis by tracking the activity of APN with high specificity and sensitivity in vivo, demonstrating its potential value for cancer diagnosis.

Ginsenoside Rg3 protects heart against isoproterenol-induced myocardial infarction by activating AMPK mediated autophagy.

BACKGROUND: Panax ginseng is a well-known medicinal herb that is widely used in traditional Chinese medicine for treating various diseases. Ginsenoside Rg3 (Rg3) is thought to be one of the most important active ingredients of Panax ginseng. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. METHODS: In the mouse heart injury model induced by isoproterenol (ISO), we used brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and caspase-3 ELISA kits to test myocardium injury. To test whether Rg3 protects myocardial injury through AMPK mediated autophagy, we used specific AMPK inhibitor in combination with Rg3. NLRP3 inflammasome related molecules such as NLRP3, ASC and caspase-1 were measured by western-blot following Rg3 treatment. RESULTS: We found that Rg3 significantly reduced ISO induced myocardial injury indicated by the downregulation of serum BNP and LDH. In addition, we showed that the improvement of myocardial injury by Rg3 was associated with enhanced expression of autophagy related protein and activation of AMPK downstream signaling pathway. CONCLUSIONS: We observed that inhibition of AMPK significantly reversed the myocardial protective effect of Rg3, which is associated with a decrease of Rg3 induced autophagy. These together suggested that Rg3 may improve myocardial injury during MI through AMPK mediated autophagy. Our study also provides important translational evidence for using Rg3 in treating myocardial infarction (MI).