叶酸修饰的载药相变纳米粒靶向治疗裸鼠移植瘤的研究

发布时间：2018-03-27 18:43

本文选题：靶向　切入点：载药　出处：《中国超声医学杂志》2017年10期

【摘要】：目的研究叶酸受体靶向的、载紫杉醇(PTX)的相变纳米粒造影剂(FR-PTX-PNPCA)对裸鼠卵巢癌移植瘤的治疗作用。方法选取载卵巢癌移植瘤的裸鼠60只,随机等分为6组,每隔3d分别通过尾静脉注射药物200μl,记录肿瘤生长情况。A组为注射生理盐水+超声,即注射生理盐水后用治疗超声辐照;B组为单纯FR-PTX-PNPCA;C组为FR-PTX-PNPCA+超声,即注射FR-PTX-PNPCA后用超声辐照;D组为非靶向的载药相变纳米粒PTX-PNPCA+超声;E组为靶向载药的非相变纳米粒FR-PTX-NPCA+超声;F组为Taxol组。于第二次给药后2h每组处死5只裸鼠,取内脏及肿瘤组织匀浆观察PTX在体内的分布情况。2周后处死剩余裸鼠,测量肿瘤大小,并将肿瘤切片作免疫组化,观察治疗效果。结果各组中肝脏和脾脏的PTX浓度最高,C组肿瘤内的PTX浓度在各组中最高;治疗后A、B、D、E组和F组肿瘤大小无明显差异,C组肿瘤较以上各组明显较小,并且C组内的肿瘤细胞增值率和凋亡率与以上各组也有显著差异。结论研究表明,经静脉注射FR-PTX-PNPCA能靶向释放药物,治疗裸鼠移植瘤,其机制可能与FR-PTX-PNPCA能靶向肿瘤细胞,并在超声作用下与相变释放药物有关,具体机制有待进一步研究。
[Abstract]:Objective to study the therapeutic effect of folate receptor-targeted, paclitaxel-loaded phase change nanoparticles (PNPCA-FR-PTX-PNPCA) on transplanted ovarian cancer in nude mice. Methods 60 nude mice carrying ovarian cancer were randomly divided into 6 groups. Every 3 days, 200 渭 l of the drug was injected through the tail vein. The growth of tumor was recorded. Group A was injected with normal saline ultrasound, and group B was irradiated by therapeutic ultrasound after injection of normal saline. Group B was treated with FR-PTX-PNPCAA C and group C was treated with FR-PTX-PNPCA ultrasound. After injection of FR-PTX-PNPCA, five nude mice were killed in each group 2 h after injection of FR-PTX-PNPCA. Group D was irradiated by ultrasound with phase change nanoparticle PTX-PNPCA as non-target carrier, group E as target drug carrying drug, group F with non-phase change nanoparticles FR-PTX-NPCA ultrasound and group F as Taxol group. 2 hours after the second administration of the drug, 5 nude mice were killed in each group, and 5 nude mice were killed in each group 2 hours after the second administration of the drug. The visceral organs and tumor homogenate were taken to observe the distribution of PTX in vivo. 2 weeks later, the remaining nude mice were killed, the tumor size was measured, and the tumor sections were stained with immunohistochemistry. Results the PTX concentration of liver and spleen in group C was the highest in each group, and the tumor size of group C was significantly smaller than that of group C after treatment, and there was no significant difference in tumor size between group E and group F after treatment. The proliferation rate and apoptosis rate of tumor cells in group C were also significantly different from those in the above groups. Conclusion the results show that intravenous injection of FR-PTX-PNPCA can target the release of drugs and treat xenograft tumors in nude mice, and its mechanism may be similar to that of FR-PTX-PNPCA targeting tumor cells. The mechanism of phase-change release drug is to be further studied.
【作者单位】：重庆医科大学附属成都第二临床学院成都市第三人民医院;
【基金】：国家自然基金青年基金项目(No.81401433)
【分类号】：R445.1;R737.31

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