iRGD肽修饰阿霉素脂质体的理化性质和对肿瘤细胞增殖抑制作用的初步研究

Physicochemical Property of iRGD Peptide Modified Doxorubicin Loaded Liposome and Its Effect on Cancer Cell Growth

中文关键词:  肺癌 iRGD 阿霉素 脂质体 整合素受体

英文关键词:Lung cancer iRGD peptide Doxorubicin Liposome Integrin receptor

中文摘要:

      目的 制备整合素分子识别配体（RGD）iRGD多肽修饰阿霉素脂质体（iRGD-LP-DOX），研究iRGD-LP-DOX的理化性质，体外肺癌细胞A549靶向性和肿瘤细胞增殖抑制率。方法 制备iRGD-LP-DOX，透射电镜观察其形态，采用透析袋法检测iRGD-LP-DOX中阿霉素的释放特点；流式细胞术检测A549细胞对iRGD-LP-DOX的摄取效率；构建肺癌A549细胞肿瘤球模型，激光共聚焦定性观察iRGD-LP-DOX 对肿瘤球的穿透能力；MTT实验检测空白脂质体和不同阿霉素剂型的细胞毒性，并计算50%抑制浓度（IC ₅₀ ）。结果 制备的iRGD-LP-DOX粒径均一，呈球形。游离DOX在5 h内全部释放，而LP-DOX和iRGD-LP-DOX 48 h内释放约40%。定量摄取实验表明A549细胞对iRGD-LP-DOX的摄取效率高于LP-DOX，差异有统计学意义（ P<0.01）；肿瘤球穿透实验结果显示iRGD-LP-DOX组的荧光强度显著强于LP-DOX组。MTT实验表明，iRGD-LP-DOX组A549细胞增殖能力受到抑制，差异有统计学意义（ P<0.01），其IC ₅₀ 值低于LP-DOX组细胞。结论 阿霉素脂质体经过iRGD修饰后，具有缓释能力，增强了DOX高效进入肿瘤细胞并抑制肿瘤细胞生长能力。

英文摘要:

      Objective To explore the protective effect and its mechanism of B7-H4 on the immuno hepatic injury. Methods The immuno hepatic injury was induced by Concanavalin A (Con A). Sixty KM mice were randomly divided into 4 groups with 15 mice in each group： Group A (saline), Group B (pcDNA3.1-mB7-H4-Fc), Group C (pcDNA3.1), Group D (Con A). One day before the injection of Con A (25 mg/kg), the mice in Group B and Group C received the injection of 100 μg pcDNA3.1-mB7-H4-Fc and 100 μg pcDNA3.1 respectively. The blood samples were collected at 12 h, 24 h and 48 h after Con A injection, the levels of ALT, AST, IL-4 and IFN-γ were measured. Five mice in each group were sacrificed at the above 3 time points, the liver tissue were harvested for histopathological detection. Results After Con A injection, the level of ALT in Group B，C, and D were higher than that in Group A. The level of ALT in Group B was lower than that in Group C and D. The significant difference was found between Group B and Group C. The hepatic injury of Group B was less serious than that of Group C and D. Conclusion B7-H4 may have protection on the immune injury of liver induced by Con A.