An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release.

BackgroundQing-dai powder (QDP), comprising Indigo naturalis (Qing-dai) and dried alum (Ku-fan), was used in Chinese medicine to treat the conditions associated with mucosal hemorrhage, such as ulcerative colitis (UC). This study aims to investigate the effects and potential mechanism of QDP on dextran sulfate sodium (DSS)-induced acute colitis in mice and to examine the regulatory effects of QDP on macrophages.MethodsSeven- to eight-week-old male C57BL/6 mice were challenged with 2.0 % DSS in drinking water for 5 days and then the colitic mice were arbitrarily allocated into five groups (n = 10 for each group). QDP (0.77, 1.54 and 3.08 g/kg) and sulfasalazine (SASP) (0.20 g/kg) were orally administered for 7 days. The disease activity index was determined by scores of body weight loss, diarrhea and rectal bleeding; histological signs of damage was analyzed by H&E staining; myeloperoxidase activity was measured by colorimetric method, levels of proinflammatory cytokines were determined by ELISA; changes in macrophages in the colon were analyzed by immunohistochemistry (IHC) and flow cytometry. Lipopolysaccharide (LPS)-induced RAW264.7 cells were treated with or without QDP, then the production of TNF-α and IL-6 were measured by ELISA; and protein molecules such as COX-2, iNOS, IкB-α were determined by Western blot.ResultsOral administration of QDP at dosages of 1.54 and 3.08 g/kg significantly reduced disease activity index on day 12 (P < 0.001 for 1.54 g/kg and P < 0.0008 for 3.08 g/kg), colon shortening (P = 0.012 for 1.54 g/kg, P = 0.001 for 3.08 g/kg), histological damage (P < 0.001 for 1.54 g/kg, P < 0.001 for 3.08 g/kg) and colonic myeloperoxidase activity (P = 0.002 for 1.54 g/kg, P < 0.001 for 3.08 g/kg) of DSS-treated mice. Moreover, QDP treatment (1.54 and 3.08 g/kg) significantly decreased DSS-induced infiltration of macrophages, and production of TNF-α (P = 0.005 for 1.54 g/kg, P = 0.002 for 3.08 g/kg), IL-1β (P = 0.008 for 1.54 g/kg, P = 0.002 for 3.08 g/kg) and IL-6 (P = 0.011 for 1.54 g/kg, P = 0.004 for 3.08 g/kg) in colonic tissues, and also reduced serum MCP-1 levels (P = 0.001 for 1.54 g/kg, P < 0.001 for 3.08 g/kg). In RAW264.7 cells, QDP significantly suppressed LPS-induced production of TNF-α and IL-6 (Both P < 0.001 for 1.0 μg/mL QDP treatment) and expression levels of COX-2 (P = 0.002 and P = 0.001 for 1 and 3 μg/mL QDP treatment, respectively) and iNOS (P < 0.001 for 3 μg/mL QDP treatment) by inhibiting IкB-α degradation (P = 0.007 and P = 0.004 for 1 and 3 μg/mL QDP treatment, respectively) and NF-кB p65 nuclear translocation.ConclusionQDP suppressed the inflammatory responses of colonic macrophages in DSS-induced UC in mice and LPS-induced RAW264.7 cells.

Background: The gut microbiome plays an important role in various cardiovascular diseases, such as atherosclerosis and hypertension, which are associated with abdominal aortic aneurysms (AAAs). Methods: Here, we used 16S rRNA sequencing to explore gut microbiota in C57BL ApoE −/− mice with AAAs. A mouse model of abdominal aortic aneurysms was induced with angiotensin II (Ang II) (1000 ng/min per kg). On day 28 after the operation, fecal samples were collected and stored at − 80°C until DNA extraction. We determined the relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding, and sequences were analyzed using a combination of mother software and UPARSE. Results: We found that the gut microbiome was different between control and AAA mice. The results of correlation analysis between AAA diameter and the gut microbiome as well as LEfSe of the genera Akkermansia, Odoribacter, Helicobacter and Ruminococcus might be important in the progression of AAAs. Conclusions: AAA mice is subjected to gut microbial dysbiosis, and gut microbiota might be a potential target for further investigation.

RNA interference (RNAi) is a highly efficient approach for gene silencing. Regulation of gene expression at post-transcriptional level provides great potential for curing diseases caused by abnormal overexpression of disease-related genes. However, the application of RNAi in the clinic has been hindered by the lack of efficient and biocompatible delivery systems. Therefore, the development of a safe and tissue-targeted double-stranded interfering RNA (siRNA) carrier for clinical application is urgently needed. Here we report the discovery of a highly efficient liposomal siRNA delivery agent based on a novel peptidomimetic built from natural amino acids. Fine tuning of the composition of amino acids, the type of amide linkage in the peptidomimetic, as well as the formulation and the physicochemical parameters of the novel lipoplex resulted in a lipid nanoparticle (LNP) that efficiently encapsulates and carries siRNA to mouse liver. In vivo experiments showed that a single injection of unmodified siRNA complexed to one of the peptidomimetics at a clinically feasible dose induced significant RNAi in mouse liver, resulting in a 90% decrease in apolipoprotein B (ApoB) mRNA level, as well as a 60% decrease in serum ApoB protein level. Analysis of mouse serum by ELISA indicated that the novel peptidomimetic based lipoplex did not elevate the level of liver enzymes (ALT, AST) in the serum. Our novel peptidomimetic-based lipoplex demonstrated great potential for the development of a safe and efficient siRNA delivery agent for clinical applications.