Advances in anti-invasive fungal drug delivery systems / 浙江大学学报·医学版

Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.

Effects of decorin on proliferation, migration and invasion of bladder cancer cells / 国际肿瘤学杂志

Objective:To investigate the effects of decorin (DCN) on the proliferation, migration and invasion of bladder cancer cells.Methods:Bladder cancer T24 cell line was used as the research object. MTT assay was used to detect the inhibitory effect of DCN at different concentrations (0, 5, 10, 20, 30, 40, 50 mg/L) on T24 cell proliferation at 24, 48, 72 and 96 h. The effects of DCN on T24 cell cycle and apoptosis were analyzed by flow cytometry. MTT assay, Transwell migration and invasion experiments were used to detect the effects of DCN on the adhesion, migration and invasion ability of T24 cells. The effects of DCN on TGF-β1 and P21 protein expression were detected by ELISA and Western blotting.Results:T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN at 24, 48, 72 and 96 h, and there were statistically significant diffe-rences in cell proliferation activity ( F=168.64, P<0.001; F=165.81, P<0.001; F=291.02, P<0.001; F=148.93, P<0.001). T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the cell proliferation activities were (60.71±3.03)%, (40.82±2.09)%, (37.24±1.63)%, (25.65±2.55)%, (23.00±2.67)%, (10.78±1.17)%, (11.04±0.96)%, respectively, and there was a statistically significant difference. At the concentration of 40 mg/L, the proliferation activity reached the lowest level, and the inhibitory effect on cell proliferation was the strongest. At concentrations of 40 and 50 mg/L, the cells in G 1 phase reached the peak value, while the cells in S phase reached the lowest value, and the cells in G 2 phase remained unchanged throughout the treatment process. T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the apoptosis rates of cells were (12.18±1.17)%, (21.24±1.05)%, (19.80±1.20)%, (26.52±1.40)%, (30.86±1.40)%, (52.99±1.22)%, (43.04±2.16)%, respectively, and there was a statistically significant difference ( F=178.54, P<0.001). The differences between 5, 10, 20, 30, 40, 50 mg/L DCN and 0 mg/L DCN were all statistically significant (all P<0.001). When T24 cells were treated with 0, 40 mg/L DCN for 72 h, the cell adhesion rates were (37.14±1.35)% and (59.86±1.95)%, the numbers of migrated cells were 53.86±3.18 and 12.86±1.35, and there were statistically significant differences ( t=25.25, P<0.001; t=31.36, P<0.001). When DCN was applied to T24 cells for 48 h, the numbers of invasion at 0, 40 mg/L were 235.14±3.44 and 160.86±3.13, and there was a statistically significant difference ( t=2.27, P<0.001). When T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, the relative expression levels of TGF-β1 were 85.67±3.35, 45.51±1.19, 49.93±4.15, 47.64±3.53, 46.05±3.18, 25.54±2.25, 33.44±4.05, and there was a statistically significant difference ( F=324.58, P<0.001). Compared with 0 mg/L DCN, 5, 10, 20, 30, 40 and 50 mg/L DCN could significantly inhibited the expression of TGF-β1 (all P<0.001). Compared with 0 mg/L DCN, P21 protein was upregulated 72 h after treatment with 40 mg/L DCN. Conclusion:DCN can inhibit proliferation and induce apoptosis of T24 cells in vitro, and has the effect of anti-metastasis of T24 cells.

Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections

As a typical human pathogenic fungus,

Progress of multi-cellular tumor spheroids culture technique for treatment of bladder cancer / 肿瘤研究与临床

Cell culture is an important tool for biological research.To better understand the pathogenesis and therapeutic methods of the tumors,the three-dimensional cell culture is applied by more and more researchers to create a culture environment that closes to the tumor microoenvironment.Thanks to the advances in the tissue engineering technology,many kinds of models of the three-dimensional cell culture achieve wide accessibility.Compared with the traditional two-dimensional cell culture,the three-dimensional cell culture is better in simulating physiological features of the human histology and cells,including cell proliferation and differentiation,the interaction of cell to cell and cell to matrix.This paper reviews the progress of multi-cellular tumor spheroids (MCTS) culture technique of the three-dimensional cell culture for treatment of bladder cancer.

Development of genetically stable recombinant Saccharomyces cerevisiae strains using combinational chromosomal integration / 生物工程学报

Chromosomal integration enables stable phenotype and therefore has become an important strategy for breeding of industrial Saccharomyces cerevisiae strains. pAUR135 is a plasmid that enables recycling use of antibiotic selection marker, and once attached with designated homologous sequences, integration vector for stable expression can be constructed. Development of S. cerevisiae strains by metabolic engineering normally demands overexpression of multiple genes, and employing pAUR135 plasmid, it is possible to construct S. cerevisiae strains by combinational integration of multiple genes in multiple sites, which results in different ratios of expressions of these genes. Xylose utilization pathway was taken as an example, with three pAUR135-based plasmids carrying three xylose assimilation genes constructed in this study. The three genes were sequentially integrated on the chromosome of S. cerevisiae by combinational integration. Xylose utilization rate was improved 24.4%-35.5% in the combinational integration strain comparing with that of the control strain with all the three genes integrated in one location. Strain improvement achieved by combinational integration is a novel method to manipulate multiple genes for genetic engineering of S. cerevisiae, and the recombinant strains are free of foreign sequences and selection markers. In addition, stable phenotype can be maintained, which is important for breeding of industrial strains. Therefore, combinational integration employing pAUR135 is a novel method for metabolic engineering of industrial S. cerevisiae strains.