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目的:考察去甲斑蝥素N-乳糖酰壳聚糖纳米粒的肝靶向抗肿瘤药效学。方法:离子诱导法制备去甲斑蝥素壳聚糖纳米粒(NCTD-CS-NPs)及去甲斑蝥素N-乳糖酰壳聚糖纳米粒(NCTD-GC-NPs);考察两种纳米粒在H22荷瘤小鼠体内的抗肿瘤活性,分别采用流式细胞仪检测及MTT法考察两种纳米粒对肝肿瘤细胞Bel-7402、肝正常细胞HL-7702的摄取和细胞毒性。结果:相同的流式测定条件下经乳糖酸修饰的纳米粒具有更强的平均荧光强度,表明其对两种细胞的亲和性更大。去甲斑蝥素(NCTD),NCTD-CS-NPs,NCTD-GC-NPs在Bel-7402中的IC50分别是(18.84±1.87),(16.38±1.48),(7.12±1.94)μg.mL-1,在HL-7702中的IC50分别是(22.66±1.74),(21.76±1.92),(12.79±1.71)μg.mL-1。2.0 mg.kg-1NCTD,NCTD-CS-NPs,NCTD-GC-NPs 3组对H22荷瘤小鼠的抑瘤率分别为28.97%,37.86%,43.56%,反映了纳米粒在H22荷瘤小鼠体内良好的肝靶向抗肿瘤活性。结论:去甲斑蝥素N-乳糖酰壳聚糖纳米粒发挥双重靶向作用,有望成为新型靶向抗肿瘤制剂。
Objective: To investigate the liver-targeted antitumor pharmacodynamics of norcantharidin N-lactosyl chitosan nanoparticles. Methods: NCTD-CS-NPs and NCTD-GC-NPs were prepared by ion-induced method. The effects of two kinds of nanoparticles on H22 tumor-bearing mice, the uptake and cytotoxicity of the two kinds of nanoparticles on the liver tumor cells Bel-7402 and liver normal cells HL-7702 were investigated by flow cytometry and MTT respectively. Results: Lactobacillus acid-modified nanoparticles have a stronger average fluorescence intensity under the same flow assay conditions, indicating greater affinity for both cells. The IC50 of Bel-7402 in NCTD, NCTD-CS-NPs and NCTD-GC-NPs were (18.84 ± 1.87), (16.38 ± 1.48) and (7.12 ± 1.94) μg.mL-1 , IC50 in HL-7702 were (22.66 ± 1.74), (21.76 ± 1.92), (12.79 ± 1.71) μg.mL-1.2.0 mg.kg-1 NCTD, NCTD- The inhibitory rates of NPs 3 to H22 tumor-bearing mice were 28.97%, 37.86% and 43.56%, respectively, which reflected the good liver-targeting anti-tumor activity of NPs in H22 tumor-bearing mice. Conclusion: Norcantharidin N-lactosyl chitosan nanoparticles play a dual role in targeting new anti-tumor agents.