Glucosamine-Modified Reduction-Responsive Polymeric Micelles for Liver Cancer Therapy.

In this work, glucose transporter-1 (GLUT-1) and glutathione (GSH) over-expression in liver cancer was utilized to design a reduction-responsive and active targeting drug delivery system AG-PEG-SS-PCL (APSP) for the delivery of sorafenib (SF). The SF-APSP micelles were prepared using the thin film hydration method and characterized by various techniques. In vitro release experiments showed that the cumulative release of SF-APSP micelles in the simulated tumor microenvironment (pH 7.4 with GSH) reached 94.76 ± 1.78% at 48 h, while it was only 20.32 ± 1.67% in the normal physiological environment (pH 7.4 without GSH). The in vitro study revealed that glucosamine (AG) enhanced the antitumor effects of SF, and SF-APSP micelles inhibited proliferation by targeting HepG2 cells and suppressing cyclin D1 expression. The in vivo antitumor efficacy study further confirmed that the SF-APSP micelles had excellent antitumor effects and better tolerance against nude mouse with HepG2 cells than other treatment groups. All in all, these results indicated that SF-APSP micelles could be a promising drug delivery system for anti-hepatoma treatment.

A novel fluorescent probe for the early detection of prostate cancer based on endogenous zinc sensing.

BACKGROUND: The early detection of prostate cancer can significantly optimize the prognosis, prolong patient lifespan, and improve quality of life. It has been well documented that prostate cancer tissues have lower zinc content than normal prostate tissues due to an impairment of the zinc accumulation mechanism. METHODS: A novel diketopyrrolopyrrole (DPP)-based fluorescent zinc ion probe named DPP-C2 was prepared. The fluorescent intensity of this novel molecule is in direct proportion to environmental zinc concentration. Malignant (DU145 and PC3 cells) and normal prostate epithelial RWPE-1 cells were tested. Prostate cancer tissues were also cultured and observed as tissue sections. The probe was also intravenously administered to tumor-bearing (DU145 and PC3 cells) nude mice and observed under a whole-body fluorescence live-imaging system. RESULTS: The probe showed minimal cytotoxicity to malignant and normal prostate cells. The RWPE-1 cells showed not only stronger baseline fluorescence but also a significant increase in signal intensity after culturing in a zinc-supplemented medium. In human prostate sections, the pathologically confirmed cancer tissues exhibited weaker fluorescence signals than normal and benign hyperplastic tissues. With proper excitation, prostate tissues revealed more intense fluorescence signals than tumor tissues, whereas other surrounding tissues showed almost no fluorescence. CONCLUSIONS: The novel zinc ion fluorescent probe DPP-C2 is low toxic and showed potential application for the early detection of prostate cancer based on endogenous zinc sensing.

Antidepressant-like effects of auraptenol in mice.

Depression is a major psychiatric disorder affecting nearly 21% of the world population and imposes a substantial health burden on society. Current available antidepressants are not adequate to meet the clinical needs. Here we report that auraptenol, an active component of the traditional Chinese medicine, angelicae dahuricae radix, had antidepressant-like effects in mice models of depression. In mouse forced swimming test and tail suspension test, two validated models of depression, auraptenol dose-dependently decreased the immobility duration within the dose range of 0.05-0.4 mg/kg. In addition, the antidepressant-like effects of auraptenol was significantly averted by a selective serotonin 5-HT1A receptor antagonist WAY100635 (1 mg/kg). These doses that affected the immobile response did not affect locomotor activity. In summary, this study for the first time identified an active component from the herbal medicine angelicae dahuricae radix that possesses robust antidepressant-like efficacy in mice. These data support further exploration for the possibility of developing auraptenol as a novel antidepressant agent in the treatment of major depression disorders.