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The Way that PEGyl-DSPC Liposomal Doxorubicin Particles Penetrate into Solid Tumor Tissue

机译:PEGyl-DSPC脂质体阿霉素颗粒渗透进入实体肿瘤组织的方式

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Background: For enhancement of drug effectiveness and reduction of drug toxicity, liposomal drugs have been studied in laboratories and clinics for decades. Although the results obtained from in vitro are encouraging, but the results from in vivo tests were not satisfactory. The main reasons for this situation were that we do not have enough information about the way how liposomal particles penetrating into solid tumor tissue, and what happening to the liposome particles after they got into the tumor tissue. In this paper, we are going to report the results from our observations on the way folic acid targeted and non-targeted PEGyl-DSPC liposomal doxorubicin particles penetrate into solid tumor tissue.Methods: Subcutaneous transplanted murine L1210JF solid tumors in mice were used as a model. PEGyl liposomal doxorubicins were injected through tail venue, and tumor tissue samples were collected at special time points. Cryosections were cut and dried by a fl owing of air after mounted on the slides right away. Then the dried cryosections were stained in water systems; the blood vessel cells were stained with green fluorescent FITC labeled antibody against CD31 antigen; the nuclei of the living cells were stained with a blue fluorescent dye DAPI. Since the whole procedure was carried out in aquatic system, the red color fluorescent liposomal doxorubicin particles remain visible under fl uorescence microscope.Results: Both folate conjugated and non-conjugated PEGyl-DSPC liposomal doxorubicin particles were only leaking out from the broken holes of blood vessels with a special direction and spread out for a limited distance, which was similar to the results showed before, in that observation a latex microsphere sample was used as a model.Abbreviations: DSPC:1, 2-Distearoyl-sn-Glycero-3-phosphatylcholine; PEG2000-DSPC:1, 2-Distearoyl-sn-Glycero 3-phosphatidylethanolamine-N-[methoxy(polyethylene glycol)-2000]; Folate-PEG3400-DSPE:1, 2-Distearoyl-sn-Glycero- 3-phosphatidylethanolamine-N-[polyethylene glycol-3400]-folate.
机译:背景:为了增强药物效力和降低药物毒性,脂质体药物已经在实验室和诊所中研究了数十年。尽管从体外获得的结果令人鼓舞,但是从体内测试获得的结果并不令人满意。造成这种情况的主要原因是,我们没有足够的信息来了解脂质体颗粒如何进入实体肿瘤组织,以及脂质体颗粒进入肿瘤组织后如何处理。本文将就叶酸靶向和非靶向PEGyl-DSPC脂质体阿霉素颗粒穿透实体瘤组织的方式报告我们的观察结果。方法:将小鼠皮下移植L1210JF实体瘤用作皮下移植小鼠模型。通过尾部部位注射PEGyl脂质体阿霉素,并在特定时间点收集肿瘤组织样品。将冷冻切片立即安装在载玻片上后,用空气对其进行切割和干燥。然后将干燥的冷冻切片在水系统中染色。用绿色荧光FITC标记的抗CD31抗原的抗体染色血管细胞。用蓝色荧光染料DAPI对活细胞的核染色。由于整个过程均在水生系统中进行,因此荧光显微镜下仍可见红色荧光脂质体阿霉素颗粒。具有特定方向的容器并以有限的距离扩展,这与之前显示的结果相似,该观察结果是使用乳胶微球样品作为模型。缩写:DSPC:1,2-Distearoyl-sn-Glycero-3 -磷脂酰胆碱; PEG2000-DSPC:1,2-二硬脂酰基-sn-甘油3-磷脂酰乙醇胺-N- [甲氧基(聚乙二醇)-2000];叶酸-PEG3400-DSPE:1,2-二硬脂酰基-sn-甘油-3-磷脂酰乙醇胺-N- [聚乙二醇-3400]-叶酸。

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