Ultrasound Combined With Active Targeting Nanoparticles In The Treatment Of Human Non-small Cell Lung Cancer

Objective:Lung cancer remained the leading cause of cancer death worldwide.Non-small cell lung cancer research is important because it is the more common histological type in Lung cancer,which has higher morbidity and mortality.In this study,docetaxel loaded PEG-albumin nanoparticles combined with ultrasound were used to treat nude mice Non-small cell lung cancer model.Also,lung cancer A549 cells were used as the main research objective,and carried out a series of experiments in vivo and in vitro,to observe the effectiveness of treatment,which hopes to provide a new way of thinking for clinical Non-small cell lung cancer treatment.Methods: 1.The human Non-small cell lung cancer(NSCLC)A549 cell line will be cultured in vitro and a part of the successfully passaged human non-small cell lung cancer A549 cells are frozen.2.Establish the subcutaneous transplanted NSCLC model and the in situ carcinoma model in nude mice: Human non-small cell lung cancer A549 cells were injected into the left armpit of 20 BALB/c nude mice to form a subcutaneous transplanted tumor model,and the changes of tumor volume and body weight were recorded.30 BALB/c nude mice were anesthetized intraperitoneally and incised at the midaxillary line(1.5 cm above the first rib line)of the left chest wall.After suturing the incision,25-30 m L of cell suspension was injected into the pleura to form an in situ NSCLC model.3.Establish the in situ NSCLC model in Nude Mice:In vivo experiments:(1)The average volume of subcutaneous tumor was about 120mm3 in nude mice and in situ tumor nude mice.Two groups of nude mice were treated with 5% glucose injection(control group),DANs,PEG-DANPs and PEG-DANPs combined with ultrasound.The single course of treatment is 7 days and4 courses,the intensity of ultrasound is 1 MHz,each time is 30 seconds.(2)All nude mice both in the subcutaneous group and in situ group were killed 2 days after the whole course of treatment.And the tumor,lung and liver were soaked in 4% neutral formaldehyde for fixation,then stained with HE.(3)TUNEL assay is used to detect the apoptosis of tumor cells,and the lung and liver tissues of nude mice in the in situ carcinoma group were subjected to HE staining and pathological semi-quantitative analysis.Results:1.Compared with other control groups,the nude mice in the US combined with PEG-DANPs group had the obviously smallest tumor mass(The level of significance was set at P<0.05;P<0.01),and their body weight maintains the best,which indicated that US combined with PEG-DANPs had the strongest ability to inhibit tumor growth and the least toxicity(P < 0.05).2.According to the pathological images of lung and liver tissues in nude mice with NSCLC,the inhibitory effect of US combined with PEG-DANPs on NSCLC in situ and anti-metastasis was the most obvious.The difference in the semi-quantitative analysis of the pathological images of lung and liver was statistically significant(P<0.05).3.According to the results of the TUNEL assay,the US combined with PEG-DANPs group has the strongest ability to induce the apoptosis of cancer cells.Conclusion:1.US combined with PEG-DANPS can effectively inhibit the growth of NSCLC,induce the apoptosis of cancer cells,and inhibit the metastasis of cancer cells,with lower toxic side effects.2.The various physical effects of US can further increase the absorption of chemotherapeutic drugs and improve targeting.3.US combined with PEG-DANPS is expected to be an effective treatment for NSCLC.