文章摘要
何 力,李 娟.HER-2靶向光敏免疫脂质体增强乳腺癌化疗效果的实验研究[J].南京医科大学学报,2017,(6):659~664
HER-2靶向光敏免疫脂质体增强乳腺癌化疗效果的实验研究
Construction and characterization of a trastuzumab Fab conjugated UV-responsive immunoliposome on improvement of tumor suppressing efficacy of chemotherapy
投稿时间:2016-07-21  
DOI:10.7655/NYDXBNS20170602
中文关键词: 乳腺癌  trastuzumab  化疗  光敏免疫脂质体  血清稳定性
英文关键词: breast cancer  trastuzumab  chemotherapy  UV-responsive immunoliposome  serum stability
基金项目:
作者单位
何 力 四川省人民医院城东病区甲状腺乳腺外科四川 成都 610000 
李 娟 四川省人民医院城东病区甲状腺乳腺外科四川 成都 610000 
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中文摘要:
      目的:构建对紫外线反应的靶向人类表皮生长因子2(human epidermal growth factor receptor 2, HER-2)的免疫脂质体,提高化疗药物对乳腺癌细胞的杀伤效果。方法:薄膜分散法制备脂质体,表面修饰上抗HER-2抗体(曲妥珠单抗)的Fab片段,并将脂质体用紫外线进行交联,制备光敏免疫脂质体。透射电镜观察脂质体的形态,动态光散射测定脂质体的粒径和血液学稳定性,倒置荧光显微镜和流式细胞术检测乳腺癌细胞MCF-7对脂质体药物的摄取能力,CCK-8试剂盒测定并比较脂质体与游离药物对乳腺癌细胞的体外杀伤效应,皮下肿瘤抑制实验比较脂质体药物与游离药物对乳腺癌细胞的体内杀伤效应。结果:本研究制备出的对紫外线敏感的HER-2靶向脂质体具有规整的球状结构、合适的粒径大小和较强的稳定性。乳腺癌细胞MCF-7对免疫脂质体的摄取能力较非靶向脂质体和游离DOX显著增强(P均<0.05)。进一步研究显示,光敏免疫脂质体药物对MCF-7细胞的体外杀伤能力明显优于非靶向脂质体药物和游离药物(P均<0.05)。体内研究结果显示,与非靶向脂质体药物和游离药物相比,免疫脂质体药物能够显著降低荷瘤小鼠的皮下肿瘤负荷(P均<0.05)。结论:本研究制备的靶向HER-2的光敏免疫脂质体拥有较好的稳定性和极强的肿瘤杀伤效果,具有广阔的临床应用前景。
英文摘要:
      Objective: To construct a UV-responsive human epidermal growth factor receptor 2 (HER-2)-targeting immunoliposome, and investigate the improvement of chemotherapy efficacy on breast cancer. Methods: We fabricated the trastuzumab Fab fragment-decorated immunoliposome by thin film-dispersion method, which formed intermolecular cross-linking through the diacetylenic group by ultra-violet (UV) irradiation. The liposomal morphology was observed with transmission electron microscope. The particle size distribution and serum stability were evaluated by dynamic light scattering. Flow cytometry was performed to compare the intracellular uptake of liposomal and free drugs. The in vitro and in vivo anti-tumor efficacy of liposomal drugs against MCF-7 cells were evaluated by CCK-8 and subcutaneous tumor inhibition analysis, respectively. Results: After UV irradiation, the immunoliposome exhibited a fine spherical structure, better serum stability and slower drug release with a decreased mean diameter of (88.1±13.2) nm. The cellular uptake of immunoliposome(PC-DOX-Fab) was significantly enhanced comparing with non-targeting liposomes(PC-DOX-BSA) and free drug(DOX)(P<0.05). Cytotoxicity assays against HER-2+ cancer cells showed that the tumor suppressing efficacy of immunoliposomal drugs was significantly improved comparing with PC-DOX-BSA and free DOX at the same condition(P<0.05). In vivo studies demonstrated that the treatment of PC-DOX-Fab significantly reduced the tumor growth compared with that of PC-DOX-BSA and free DOX (P<0.05). Conclusion: In this study, we identified a novel liposomal drug delivery system for improved chemotherapy against HER-2-positive breast cancer cells, which owned a fine spherical structure and excellent serum stability. The in vitro and in vivo experimental results clearly suggested that this UV-responsive immunoliposome exhibits potent tumor suppressing activities, which deserved further investigation for clinical application.
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