Targeting Anti-ICAM-1 Containing Imatinib And Liquid Fluorocarbon Liposomes For The Treatment Of Endotoxin-induced Acute Respiratory Distress Syndrome Mouse Model

ObjectiveTo prepare targeted anti-ICAM-1 liposomes loading imatinib and liquid fluorocarbon,detect liposome size and other basic characteristics,and investigate the therapeutic effect of the liposomes on ALI/ARDS mice.MethodsThe anti-ICAM-1 liposomes were prepared by the rotary evaporation method,and the particle size was detected by Malvin particle size analyzer.The drug loading in the liposomes was observed under the perspective of electron microscope.The morphology was observed under light microscope.The phase transformation was observed at constant temperature heating plate at 37.5?,and the release rate of the liposomes was observed in vitro.The 30 6-8 weeks C57BL/6 mice were randomly divided into control group,LPS model group,targeting anti-ICAM-1liposomes treatment group,one day later,observe lung HE staining of paraffin sections and distribution of ICAM-1 immunity fluorescence in lung paraffin section,lung tissue mRNA was extracted,qRT-PCR detectionof IL-6,IL-8,IL-10,TNF-a mRNA expression,compared mice lung wet to dry weight ratio and mice alveolar fluid clearance.Targeted anti-ICAM-1liposomes and non-targeted liposomes were injected into ALI/ARDS mice by tail vein.All organs were frozen sectioning,and the distribution of two groups of liposomes in various organs was observed under confocal microscope.ResultsTarget anti-ICAM-1 liposomes loading imatinib and liquid fluorocarbon were successfully prepared,with a particle size of320.8±58.7nm.Under the transmission electron microscope,the drug was successfully encapsulated inside them.Under the light microscope,the size of liposomes was even,and liposomes were observed under light microscope at 37.5?.The release of liposomes peak at 12 h was reached and the release curve of liposome drugs was obtained.Compared with control group,LPS group had ARDS typical pathological features,lung injury obviously,pathological score increased(P<0.01),IL-8,IL-6,TNF-a increased(P<0.001),IL-10 reduced(P<0.05).The wet dry weight ratio(W/D)increased(P<0.01)and the alveolar fluid clearance(AFC)decreased significantly(P<0.01).Targeted anti-ICAM-1 liposomes treatment group,the pathological score decreased(P<0.05),IL-8 IL-6,TNF-a decreased(P<0.05),IL-10 increased(P<0.05).The wet dry weight ratio(W/D)decreased(P<0.05)and AFC improved(P<0.05).ConclusionTargeted anti-ICAM-1 liposomes loading imatinib and liquid fluorocarbon have obvious therapeutic effect on LPS induced ALI/ARDS mice.Objective TMEM16 A also known as ANO1(anoctamin-1)was reported to be vital in the growth and invasion of several malignancies.However,the role of TMEM16 A in lung cancer remained unclear.The aim of this study was to evaluate the expression of TMEM16 A and Its significance in lung cancer.Methods q RT-PCR and Western blot were performed to evaluate the TMEM16 A m RNA and protein expression.Proliferation and invasion of H1299 cancel cells were evaluated by CCK-8 and transwell assays.Tumor volumes in nude mice implanted with H1299 cells were assessed once every week for a total period by measuring two perpendicular dimensions.Immunofluorescence staining revealed expression of TMEM16 A in nude mice cancer tissues.The experiment was completed at Chongqing Medical University in 2017Results Our findings provided compelling evidence that TMEM16 A production in H1299 cells is 2.1 times higher than that of in HBE16 cells.We showed that overexpression of TMEM16 A contributed to the proliferation of H1299 cells.Moreover,T16Ainh-A01,a specific TMEM16 A inhibitor or sh RNA targeting TMEM16 A somewhat inhibited lung tumor cell growth and invasion as evident from in vitro studies,and from in vivo xenograft-tumor growth.Inhibition of TMEM16 A strongly suppressed EGFR phosphorylation and growth of lung cancer cells.Furthermore,a reduction of p-RAS and p-ERK1/2 was also observed.Conclusion TMEM16 A promoted growth and invasion in lung cancer cells via an EGFR/ MAPK-dependent signaling pathway.So we infer TMEM16 A membrane protein may have potential to serve as a biomarker in lung cancer.