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叶酸修饰的聚轮烷衍生物传递siRNA-CD47对黑色素瘤增殖的作用

Folic acid modified polyrotaxanes effectively transfer si RNA-CD47 to inhibit the proliferation of melanoma

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【作者】 朱莉娜李悦山周毅王赫陈建海

【Author】 ZHU Li-na;LI Yue-shan;ZHOU Yi;WANG He;CHEN Jian-hai;College of Pharmaceutics Science, Guangzhou Medical University;The Second Affiliated Hospital of Guangzhou Medical University;Nanfang Hospital, Southern Medical University;

【机构】 广州医科大学药学院广州医科大学附属第二医院南方医科大学南方医院

【摘要】 本文探索了叶酸修饰的聚轮烷衍生物(FPP)传递si RNA-CD47抑制黑色素瘤增殖的作用。采用Western blot、RT-PCR检测临床黑色素瘤患者病灶组织CD47的表达;马尔文粒径仪、扫描电镜检测FPP(si RNA-CD47:CD47)纳米粒的物理性能;克隆形成实验检测FPP(CD47)纳米粒对细胞克隆的影响;侵袭实验检测FPP(CD47)对B16F10细胞转移的影响;荷瘤小鼠实验检测FPP(CD47)对肿瘤增殖的影响。结果表明,临床黑色素瘤患者CD47表达较正常对照组织显著升高;FPP(CD47)纳米粒粒径为80 nm,电位10 m V;与FPP(Con)相比,FPP(CD47)治疗组中CD47荧光强度显著性减少到4.2%;B16F10细胞克隆形成减少了91%;同时,FPP(CD47)组中荷瘤小鼠瘤体积显著减少了90%,并且降低瘤中CD47的蛋白和m RNA表达。FPP传递si RNACD47进入细胞可有效抑制黑色素瘤增殖。

【Abstract】 To investigate the effect that folic acid-modified polyrotaxanes(FPP) transfered si RNA CD47 to inhibit melanoma proliferation, the expression of CD47 in clinical melanoma patients was tested by Western blot and RT-PCR, respectively. Physical performance of FPP(si RNA-CD47: CD47) nanoparticles was tested by Malvern particle size instrument and scanning electron microscope. The clone formation experiment demonstrated that FPP(CD47) nanoparticles inhibited the growth of clones. Invasion assay revealed that FPP(CD47) inhibited migration of B16F10 cells. Tumor bearing mice were used in the experiment to test the efficacy of FPP(CD47) treatment. Compared with the control group, high expression of CD47 was observed in the clinical melanoma patients. FPP(CD47) nanoparticle size at 80 nm exhibited a potential of 10 m V; compared with FPP(Con), fluorescence intensity was significantly reduced to 4.2% and B16F10 cell clone formation was decreased by 91% in the FPP(CD47) treatment. Tumor volume of tumor-burdened mice was decreased by 90% with FPP(CD47) treatment. FPP(CD47) lowered CD47 protein and m RNA expression in the tumor. This study suggests that FPP may transfer si RNA CD47 into the cancer cells to inhibit melanoma growth effectively.

【基金】 广东省自然科学基金资助项目(2014A030310022);广州市科学研究专项资助项目(201510010212)
  • 【文献出处】 药学学报 ,Acta Pharmaceutica Sinica , 编辑部邮箱 ,2016年03期
  • 【分类号】R739.5
  • 【被引频次】1
  • 【下载频次】233
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