多功能嵌合肽T7-R8/DNA纳米复合物的制备及其抑制黑色素瘤的体外细胞学研究  

Preparation of Multifunctional Chimeric Peptide T7-R8/DNA Nanocomplexes and Evaluation of Inhibiting Melanoma Cells in Vitro

作　　者：谭娇 谢曌璐 苏湲淇[1,2] 刘小东 郑小红 刘巧[1,2] TAN Jiao;XIE Zhao-lu;SU Yuan-qi;LIU Xiao-dong;ZHENG Xiao-hong;LIU Qiao(Chongqing Medical and Pharmaceutical College,Chongqing 401331,China;Chongqing Engineering Research Center of Pharmaceutical Sciences,Chongqing 401331,China;Department of Pharmacy,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China􀀽􀁝􀀽􀁤)

机构地区：[1]重庆医药高等专科学校药学院,重庆401331 [2]重庆市药物制剂工程技术研究中心,重庆401331 [3]重庆医科大学附属第二医院药学部,重庆400010

出　　处：《中国药学杂志》2021年第2期122-127,共6页Chinese Pharmaceutical Journal

基　　金：重庆市自然科学基金项目资助(cstc2018jcyjAX0722);重庆市教委科学技术研究项目资助(KJQN201802805);重庆医药高等专科学校自然科学技术研究项目资助(ygz2018110)。

摘　　要：目的合成具有肿瘤靶向作用、穿膜能力和药物载体功能的嵌合肽T7-R8,制备安全有效的T7-R8/pTRAIL纳米复合物,初步研究其对小鼠黑色素瘤B16F10细胞的增殖抑制作用。方法采用标准固相合成法合成多功能嵌合肽T7-R8,共孵育法制备T7-R8/pTRAIL纳米复合物,并对其理化性质进行评价,用流式细胞仪检测细胞转染效率,用CCK-8法检测抑制黑色素瘤细胞增殖的能力。结果当T7-R8/pTRAIL质量比≥10时,带正电的T7-R8载体可以完全压缩pTRAIL形成稳定的纳米复合物,选择最佳质量比(WT7-R8/WpTRAIL=20∶1)用于抗黑色素瘤增殖实验,经过T7肽修饰后,发现T7-R8/pTRAIL纳米复合物对黑色素瘤增殖抑制作用强于R8/pTRAIL纳米粒(P<0.05)。结论T7-R8/pTRAIL纳米复合物可能是一种高选择性、高效的抗黑色素瘤给药系统,为后续的治疗研究提供新的思路。OBJECTIVE To design and synthesize Achimeric peptide T7-R8 with tumor targeting ability,cell penetrating ability and drug carrier function and evaluate the inhibitory activity of the proliferation of B16F10 cells.METHODS The multifunctional chimeric peptide T7-R8 was synthesized by standard solid phase synthesis,followed by electrostatic interaction with pTRAIL.The physicochemical properties of T7-R8/pTRAIL were evaluated.The cell transfection efficiency was examined by flow cytometry and the proliferation inhibition of B16F10 cells was evaluated by CCK-8 assay.RESULTS Cationic T7-R8 carrier could be fully condensed with pTRAIL to form the stable nanocomplexes when the mass ratio≥10.The nanocomplexes with the best mass ratio(WT7-R8/WpTRAIL=20∶1)was evaluated for the anti-melanoma proliferation activity.The in vitro cytotoxicity experiments demonstrated that the T7-R8/pTRAIL nanocomplexes was significantly more active than R8/pTRAIL nanocomplexes(P<0.05).The B16F10 cell cytotoxicity activity were increased by modification of T7 peptide.CONCLUSION T7-R8/pTRAIL nanocomposites could be a highly selective and efficient anti-melanoma drug delivery system,providing a new approach for the following treatment research.

关 键 词：转铁蛋白受体 基因治疗 嵌合肽 黑色素瘤 药物载体 

分 类 号：R944[医药卫生—药剂学]