Quaternized carbon quantum dots with broad-spectrum antibacterial activity for the treatment of wounds infected with mixed bacteria.

Bacterial resistance to antibiotics have become one of the most severe threats in global public health, so the development of new-style antimicrobial agents is urgent. In this work, quaternized carbon quantum dots (qCQDs) with broad-spectrum antibacterial activity were synthesized by a simple green "one-pot" method using dimethyl diallyl ammonium chloride and glucose as reaction precursors. The qCQDs displayed satisfactory antibacterial activity against both Gram-positive and gram-negative bacteria. In rat models of wounds infected with mixed bacteria, qCQDs obviously restored the weight of rats, significantly reduced the death of rats from severe infection, and promoted the recovery and healing of infected wounds. Biosafety tests confirmed that qCQDs had no obvious toxic and side effects during the testing stage. The analysis of quantitative proteomics revealed that qCQDs mainly acted on ribosomal proteins in Staphylococcus aureus (Gram-positive bacteria) and significantly down-regulated proteins associated with citrate cycle in Escherichia coli (Gram-negative bacteria). Meanwhile, real-time quantitative PCR confirmed that the variation trend of genes corresponding to the proteins associated with ribosome and citrate cycle was consistent with the proteomic results after treatment of qCQDs, suggesting that qCQDs has a new antibacterial mechanism which is different from the reported carbon quantum dots with antibacterial action. STATEMENT OF SIGNIFICANCE: With the development of the research on carbon quantum dots, the application of carbon quantum dots in the field of medicine has attracted extensive attention. In this paper, quaternized carbon quantum dots (qCQDs) with antimicrobial activity prepared by specific methods were studied, including antimicrobial spectrum, antimicrobial mechanism and in vivo antimicrobial application. The antimicrobial mechanism of qCQDs was studied by proteomics and RT-qRCR, and the different mechanisms of qCQDs against Gram-positive and Gram-negative bacteria were also found. This study provides a research foundation for the application of carbon quantum dots in antimicrobial field, and also expands the application range of carbon quantum dots in medicine field.

Proliposomes for oral delivery of total biflavonoids extract from Selaginella doederleinii: formulation development, optimization, and in vitro-in vivo characterization.

PURPOSE: Amentoflavone, robustaflavone, 2'',3''-dihydro-3',3'''-biapigenin, 3',3'''-binaringenin and delicaflavone are five major active ingredients in the total biflavonoids extract from Selaginella doederleinii (TBESD) with favorable anticancer properties. However, the natural-derived potent antitumor agent of TBESD is undesirable due to its poor solubility. The present study was to develop and optimize a proliposomal formulation of TBESD (P-TBESD) to improve its solubility, oral bioavailability and efficacy. MATERIALS AND METHODS: P-TBESD containing a bile salt, a protective hydrophilic isomalto-oligosaccharides (IMOs) coating, were successfully prepared by thin film dispersion-sonication method. The physicochemical and pharmacokinetic properties of P-TBESD were characterized, and the antitumor effect was evaluated using the HT-29 xenograft-bearing mice models in rats. RESULTS: Compared with TBESD, the relative bioavailability of amentoflavone, robustaflavone, 2'',3''-dihydro-3',3'''-biapigenin, 3',3'''-binaringenin and delicaflavone from P-TBESD were 669%, 523%, 761%, 955% and 191%, respectively. The results of pharmacodynamics demonstrated that both TBESD and P-TBESD groups afforded antitumor effect without systemic toxicity, and the antitumor effect of P-TBESD was significantly superior to that of raw TBESD, based on the tumor growth inhibition and histopathological examination. CONCLUSION: Hence, IMOs-modified proliposomes have promising potential for TBESD solving the problem of its poor solubility and oral bioavailability, which can serve as a practical oral preparation for TBESD in the future cancer therapy.

Antibacterial mechanism of Tetrastigma hemsleyanum Diels et Gilg's polysaccharides by metabolomics based on HPLC/MS.

Tetrastigma hemsleyanum Diels et Gilg (THDG) is used as a Chinese traditional anti-inflammatory medicine for about thousands of years. In this work, Tetrastigma hemsleyanum Diels et Gilg's polysaccharide (TP) can inhibit E. coli's growth in initial dosing period. Compared with the antibacterial effect of Achyranthe's polysaccharide (AP) from their metabolic profile, it's obviously that their metabolic sites for E. coli were inconsistent. Moreover, TP could not only increase the level of fructose-6-phosphate (F6P), decrease the level of fructose-1,6-diphosphate (FBP), but also charge the amount of the two differential metabolic with the change of the concentration and the dosing time. Actually, F6P could transform into FBP by catalyze of 6-phosphofructokinase-1(6-PFK-1), which is an important process in glycolysis. Furthermore, FBP was considered have positively correlated with E. coli's growth rate. Therefore, TP can inhibit the E. coli's proliferation by interfering with the process for glycolysis and gluconeogenesis. Based on the experimental result, we proposed a new mouthwash method to evaluate the anti-bacterial activity. Compared with AP, TP can inhibit the E. coli's growth within 2 h with a low concentration (0.5%) and a short dosing time (5 min). This study extends the applications of THDG and establishes a new assessment method for the pharmacology activity of Chinese herbal medicine.

Nitrogen-doped carbon quantum dots as an antimicrobial agent against Staphylococcus for the treatment of infected wounds.

Antimicrobial resistance is becoming more and more serious and has become a potential hazard to human life and health. The fabrication of some new antibacterial substances against resistant bacteria is demanded. With the wide application and research of carbon nanomaterials, nitrogen-doped carbon quantum dots (NCQDs) were synthesized by a one-step chemical route herein. The particle size of NCQDs in the range of 2-5 nm were characterized by transmission electron microscopy (TEM), atomic force microscopy, and dynamic light scattering. The functional groups and optical properties of NCQDs were investigated by UV-vis absorption spectroscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Disk-diffusion tests showed that the NCQDs had specific antibacterial activity against Staphylococcus. TEM showed that the NCQDs could destroy the cell structure of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) but could not combat Escherichia coli. The antibacterial mechanism may be that positively charged NCQDs firstly interacted with the negatively charged bacteria, and then specifically anchored on some specific sites on the surface of Staphylococcus. The NCQDs were applied to treat wounds infected with MRSA and showed the same therapeutic effect as vancomycin. Photomicrographs of hematoxylin-eosin-stained histological sections showed that the NCQDs at concentrations effectively killing S. aureus and MRSA caused negligible toxicity to the main rat organs, including heart, liver, spleen, lung, and kidney. Thus, the NCQDs can be developed as a promising antibacterial agent for Staphylococcus. And the NCQDs are likely to treat local infections caused by Staphylococcus clinically, especially S. aureus and MRSA.