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。
Abstract
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
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Key words
transferrin receptor /
gene therapy /
chimeric peptide /
melanoma /
drug carrier
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中图分类号：
R944
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参考文献
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脚注
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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)
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