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目的:制备一种具有靶向新生血管特点的载TNP-470纳米粒,观察其对人脐静脉内皮细胞(HUVECs)的靶向性及增殖的影响,观察其对肿瘤组织的靶向性以及治疗效果。方法:采用单乳法制备载TNP-470纳米粒,并将其共价偶联血管内皮生长因子(VEGF),命名为TNP-470-NPs-VEGF。透射电镜下观察TNP-470-NPs-VEGF的形态,纳米粒度分析仪检测其大小。CCK-8试剂盒检测对HUVECs的细胞毒作用,荧光显微镜观察HUVECs对纳米粒的摄取。观察静脉注射后对肿瘤的靶向性,以及对荷瘤裸鼠的治疗效果。结果:TNP-470-NPs-VEGF形态近似球形,直径为115～130nm。细胞摄取结果显示,VEGF修饰的纳米粒能明显被细胞所摄取,且呈浓度依赖性;CCK-8结果显示,VEGF修饰的载TNP-470靶向纳米粒能够明显抑制HUVECs细胞的生长,且呈浓度依赖性。SKOV3荷瘤裸鼠体内实验发现,TNP-470-NPs-VEGF的肿瘤靶向性好,能显著抑制肿瘤的生长。结论:成功制备得到的TNP-470-NPs-VEGF,能显著增强HUVECs细胞的摄取,抑制细胞增殖,对裸鼠体内的人卵巢癌SKOV3肿瘤具有明显的靶向性,能显著抑制肿瘤的生长。
OBJECTIVE: To prepare a new type of TNP-470 nanoparticle with the characteristics of targeting neovascularization and observe its effect on the targeting and proliferation of human umbilical vein endothelial cells (HUVECs). To observe its targeting on tumor tissue and its therapeutic effect effect. METHODS: TNP-470 nanoparticles were prepared by single emulsion method and were covalently coupled to vascular endothelial growth factor (VEGF) and named as TNP-470-NPs-VEGF. The morphology of TNP-470-NPs-VEGF was observed under transmission electron microscope, and its size was measured by nano-particle size analyzer. CCK-8 kit was used to detect the cytotoxic effect on HUVECs. The uptake of nanoparticles by HUVECs was observed by fluorescence microscopy. Observe the targeting of the tumor after intravenous injection, as well as the therapeutic effect on tumor-bearing nude mice. Results: The morphology of TNP-470-NPs-VEGF was approximately spherical with a diameter of 115-130 nm. The results of cell uptake showed that the VEGF-modified nanoparticles were significantly uptake by cells and in a concentration-dependent manner. The results of CCK-8 showed that VEGF-modified TNP-470 loaded nanoparticles could significantly inhibit the growth of HUVECs Concentration dependence. In vivo experiments of SKOV3 tumor-bearing nude mice showed that tumor targeting of TNP-470-NPs-VEGF is good and can significantly inhibit tumor growth. Conclusion: The successfully prepared TNP-470-NPs-VEGF can significantly upregulate the uptake of HUVECs and inhibit the proliferation of human ovarian cancer SKOV3 in nude mice, which can significantly inhibit tumor growth.