An oral polyphenol host-guest nanoparticle for targeted therapy of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a global public health challenge that affects millions of people. Current medical treatments for IBD are not fully effective and may cause undesirable side effects on patients. Thus, there is an urgent need for safe, simple, and efficacious strategies to treat IBD in clinical settings. Here, we develop an oral polyphenol nanoparticle (PDT) by assembling dexamethasone sodium phosphate (DSP)-loaded poly-ß-cyclodextrin with tannic acid via host-guest interactions for treating IBD. This one-step assembly process is rapid (within 10 s), reproducible, and free of harmful chemical agents, which can facilitate its clinical translation. PDT is negatively charged due to the three components, which enable it to specifically target the positively charged inflamed colonic mucosa through electrostatic attraction, thus localizing the drug at the inflamed site to reduce systemic exposure and side effects. Furthermore, PDT exhibits a strong reactive oxygen species (ROS)-scavenging ability derived from the tannic acid component, which can alleviate ROS-mediated inflammatory responses and ameliorate IBD symptoms. Compared with free DSP, PDT demonstrates sustained DSP release behavior in vitro and in vivo, as well as enhanced therapeutic efficacy in a colitis mouse model. These results suggest that PDT might be a potential therapeutic agent for the treatment of IBD. Moreover, this facile polyphenol host-guest assembly strategy may provide a promising drug-delivery platform for treating various diseases STATEMENT OF SIGNIFICANCE: To develop safe and effective treatments for inflammatory bowel disease (IBD), we have designed an oral polyphenol nanoparticle (PDT) using the host-guest assembly of dexamethasone sodium phosphate (DSP)-loaded poly-ß-cyclodextrin with tannic acid. Through in vitro and in vivo experiments, PDT has demonstrated remarkable inflammation-targeting, ROS-scavenging, and anti-inflammatory properties, along with sustained release of DSP. Moreover, in an IBD mouse model, PDT has shown significantly improved therapeutic efficacy compared to free DSP. The host-guest assembly strategy employed for PDT is noteworthy for its rapidity, reproducibility, and safety due to the absence of harmful chemicals, holding great promise for designing a diverse range of nanomedicines customized for treating various diseases.

One-Step Assembly of Versatile Multifunctional Coatings Based on Host-Guest and Polyphenol Chemistry.

Developing a facile, efficient, and versatile polyphenol coating strategy and exploring its novel applications are of great significance in the fields of material surfaces and interfaces. Herein, a one-step assembly strategy for constructing novel tannic acid (TA) coatings via a solvent evaporation method is reported using TA and polycyclodextrin (PCD) particles (TPP). TPP with a high phenolic group activity of 88% integrates the advantages of host-guest and polyphenol chemistry. The former can drive TPP dynamically assemble into a large and collective aggregation activated by high temperature or density, and the latter provides excellent adhesion properties to substrates (0.9 mg cm-2 ). TPP can assemble into a coating (TPC) rapidly on various substrates within 1 h at 37 °C while with a high availability of feed TPP (≈90%). The resulting TPC is not only high-temperature steam-sensitive for use as an anti-fake mask but also pH-sensitive for transforming into a free-standing film under physiological conditions. Moreover, various metal ions and functional particles can incorporate into TPC to extend its versatile properties including antibacterial activity, enhanced stability, and conductivity. This work expands the polyphenol coating strategy and builds up a one-step and efficient preparation platform of polyphenol coating for multiapplication prospects in various fields.

Hexokinase II inhibitor, 3-BrPA induced autophagy by stimulating ROS formation in human breast cancer cells.

Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, has been proposed as a specific antitumor agent. Autophagy is a process that regulates the balance between protein synthesis and protein degradation. Autophagy in mammalian systems occurs under basal conditions and can be stimulated by stresses, including starvation, oxidative stress. Therefore, we hypothesized that 3-BrPA could induce autophagy. In the present study, we explored the mechanism of 3-BrPA and its combined action with chloroquine. Our results demonstrate that in MDA-MB-435 and in MDA-MB-231 cells, 3-BrPA induces autophagy, which can be inhibited by chloroquine. Furthermore, the combined treatment synergistically decreased the number of viable cells. Interestingly, the combined treatment triggered apoptosis in MDA-MB-435 cells, while it induced necroptosis in MDA-MB-231 cells. ROS mediated cell death when 3-BrPA and CQ were co-administered. Finally, CQ enhanced the anticancer efficacy of 3-BrPA in vivo. Collectively, our results show that 3-BrPA triggers autophagy, increasing breast cancer cell resistance to 3-BrPA treatment and that CQ enhanced 3-BrPA-induced cell death in breast cancer cells by stimulating ROS formation. Thus, inhibition of autophagy may be an innovative strategy for adjuvant chemotherapy of breast cancer.human skeletal muscle. Efficient Mirk depletion in SU86.86 pancreatic cancer cells by an inducible shRNA decreased expression of eight antioxidant genes. Thus both cancer cells and differentiated myotubes utilize Mirk kinase to relieve oxidative stress.

[Effect of 3-bromopyruvate on mitochondrial membrane potential and apoptosis of human breast carcinoma SK-BR-3 cells].

OBJECTIVE: To study the effect of glycolysis inhibitor 3-bromopyruvate (3-BrPA) in inducing apoptosis of human breast carcinoma cells SK-BR-3 and the possible mechanism. METHODS: MTT assay was used to detect the growth inhibition induced by 3-BrPA in breast cancer cells SK-BR-3. The apoptotic cells were detected by flow cytometry with propidium iodide (PI). ATP levels in the cells were detected by ATP assay kit, and DHE fluorescent probe technique was used to determine superoxide anion levels; the mitochondrial membrane potential was assessed using JC-1 staining assay. RESULTS: MTT assay showed that the proliferation of SK-BR-3 cells was inhibited by 3-BrPA in a time- and concentration-dependent manner. Exposure to 80, 160, and 320 µmol·L(-1) 3-BrPA for 24 h resulted in cell apoptosis rates of 6.7%, 22.3%, and 79.6%, respectively, and the intracellular ATP levels of SK-BR-3 cells treated with 80, 160, 320 µmol·L(-1) 3-BrPA for 5 h were 87.7%, 60.6%, and 23.7% of the control levels. 3-BrPA at 160 µmol·L(-1) increased reactive oxygen levels and lowered mitochondrial membrane potential of SK-BR-3 cells. CONCLUSION: 3-BrPA can inhibit cell proliferation, reduce the mitochondrial membrane potential and induce apoptosis in SK-BR-3 cells, the mechanism of which may involve a reduced ATP level by inhibiting glycolysis and increasing the reactive oxygen level in the cells.