Background: Neutrophil-based drug delivery system possesses excellent advantages in targeting at tumour because neutrophils are easily recruited by chemotactic factor in tumor microenvironment. Herein, we developed a novel tactic of multistage neutrophils-based nanoparticle delivery system for promoting photothermal therapy (PTT) of lung cancer. Results: Au nanorod (AuNR) was successfully modified with bovine serum albumin (AuNRB) and further conjugated with RGD (AuNRBR), followed by neutrophil internalisation to obtain neutrophils-based delivery system (AuNRBR/N). The engineered neutrophils efficiently migrated across the epithelial cells due to inflammatory signal. They exhibited better toxicity against Lewis cells with laser irradiation in vitro. Moreover, AuNRBR/N showed significantly more targetability to tumour tissue compared with cell carrier-free AuNRBR, as demonstrated in Lewis tumour-bearing mice. The enhanced tumour homing efficiency of AuNRBR/N together with subsequently released AuNRBR from the neutrophils was favourable for further deep tissue diffusion and contributed to the inhibition of the tumour growth in PTT and improved survival rate (over 120 days). Conclusions: Overall results illustrated that the design of cell-based nanoparticle delivery system for PTT of cancer is promising.
1 November 2017 in Allergologia et Immunopathologia
We aimed to observe the effect of icariin on an asthma mouse model and explore the potential underlying mechanisms. The asthma mouse model was established by ovalbumin (OVA) sensitisation and respiratory syncytial virus (RSV) infection and then treated with icariin. Airway resistance was assessed by whole body plethysmograph. In addition, pathological slides were stained with haematoxylin-eosin, and the peribronchial inflammation was observed microscopically. The concentration of prostaglandin D2 (PGD2) in serum and bronchoalveolar lavage fluid (BALF) was detected by enzyme-linked immuno sorbent assay (ELISA). The relative level of prostaglandin D2 receptor 2 (CRTH2) mRNA was assessed by real-time quantitative PCR. Compared with the icariin-untreated group, there was a significant reduction of Penh in the treated group. Total leucocyte amount and all sorts of leukocytes were lower in the treated group than in the untreated group. HE staining results revealed that a large number of inflammatory cells infiltrated into the peribronchial tissues of untreated group, and the degree of airway inflammation decreased significantly in the treated group. PGD2 in serum and BALF, as well as CRTH2 mRNA level in lung tissues were lower in the treated group than in the untreated group. Icariin is a promising therapeutic strategy for asthma, and PGD2 might be a new target for asthma therapy in OVA-induced and RSV-infected asthma model.
1 November 2015 in Allergologia et Immunopathologia
Asthma is a chronic inflammatory airway disease, the incidence of which has increased recently. In order to identify the potential biomarkers for allergic asthma therapy, microarray data were analysed to find meaningful information. Microarray data GSE18965 were downloaded from Gene Expression Ominibus (GEO), including seven asthmatic epithelium samples from children with allergic asthma and nine healthy controls. Limma package was used to detect differentially expressed genes (DEGs) and the criteria were |log fold change|>0.5 and p value<0.05. We used Database for Annotation, Visualization and Integrated Discovery (DAVID) tool to perform GO function and KEGG pathway analysis. STRING database was used to construct protein-protein interaction (PPI) network. MicroRNA (miRNA) regulation network was constructed according to miRecords database. We identified 274 DEGs in asthma epithelium samples comparing with healthy controls. There were 123 up-regulated DEGs and 151 down-regulated DEGs. PPI network analysis showed that TSPO, G6PD and TXN had higher degree. miRNA regulation network demonstrated that miR-16 and miR-15a had higher degree. The target genes of miRNAs were significantly enriched in the apoptosis function. TSPO, G6PD and TXN, miR-16, miR-15a and apoptosis may be used as the targets for children's allergic asthma therapy.
Non‑small‑cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases, with a 5‑year survival rate of <15%. 1‑O‑acetylbritannilactone (ABL), a natural chemical component obtained from inula britannica, a Chinese traditional medicine, has been demonstrated to have anticancer activity. In the present study, the antiproliferative and proapoptotic abilities of ABL alone or in combination with gemcitabine in a human NSCLC cell line were investigated. A549 cells were treated in vitro with ABL, gemcitabine, and a combination of ABL and gemcitabine for 72 h. The results demonstrated that ABL and gemcitabine inhibited cell growth and induced apoptosis of A549 cells. These effects were more potent following the combination of ABL and gemcitabine treatment than either agent alone. Furthermore, the signal transduction analysis revealed nuclear factor (NF)‑κB expression was significantly decreased by ABL and the combination treatment. The inhibitor nuclear factor κBα (IκBα) and Bax levels were upregulated whereas Bcl‑2 was substantially downregulated following treatment. The present findings suggest that ABL combined with gemcitabine elicits potent apoptosis of lung cancer cells and therefore, ABL has the potential to be developed as a chemotherapeutic agent.
Background : Neutrophil-based drug delivery system possesses excellent advantages in targeting at tumour because neutrophils are easily recruited by chemotactic factor in tumor microenvironment. Herein, we developed a novel tactic of multistage neutrophils-based nanoparticle delivery system for promoting photothermal therapy (PTT) of lung cancer. Results: Au nanorod (AuNR) was successfully modified with bovine serum albumin (AuNRB) and further conjugated with RGD (AuNRBR), followed by neutrophil internalisation to obtain neutrophils-based delivery system (AuNRBR/N). The engineered neutrophils efficiently migrated across the epithelial cells due to inflammatory signal. They exhibited better toxicity against Lewis cells with laser irradiation in vitro . Moreover, AuNRBR/N showed significantly more targetability to tumour tissue compared with cell carrier-free AuNRBR, as demonstrated in Lewis tumour-bearing mice. The enhanced tumour homing efficiency of AuNRBR/N together with subsequently released AuNRBR from the neutrophils was favourable for further deep tissue diffusion and contributed to the inhibition of the tumour growth in PTT and improved survival rate (over 120 days). Conclusions: Overall results illustrated that the design of cell-based nanoparticle delivery system for PTT of cancer is promising.