Spider Toxin Peptide Lycosin-I Functionalized Gold Nanoparticles for in vivo Tumor Targeting and Therapy.

Spider Toxin Peptide Lycosin-I Functionalized Gold Nanoparticles for in vivo Tumor Targeting and Therapy.
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用于体内肿瘤靶向和治疗的蜘蛛毒素肽 Lycosin-I 功能化金纳米颗粒

DOI:
10.7150/thno.19780
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发表时间:
2017
期刊:
影响因子:
12.4
通讯作者:
Liu Z
Liu Z
中科院分区:
医学1区
文献类型:
--
作者:
Tan H;Huang Y;Xu J;Chen B;Zhang P;Ye Z;Liang S;Xiao L;Liu Z

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细胞穿透肽(cellpenetratingpeptides,CPPs)是一种常用的功能性物质,可通过细胞内传递绕过生物膜屏障。然而,CPP的进一步应用由于缺乏对靶细胞的选择性而受到阻碍。蜘蛛毒肽lycosin-I是一种对癌细胞具有较强细胞毒性的CPP,它可能使lycosin-I选择性地将功能性物质递送到癌细胞中。在这项研究中,我们证明了lycosin-I-conjugated spherical gold nanoparticles(LGNP)不仅对癌细胞表现出有效的细胞内化效率,而且对非癌细胞表现出前所未有的选择性。虽然LGNP通过网状内皮系统主导的清除模式从活循环系统中去除,对动物没有明显的不良影响,但它们实际上显示出活性的肿瘤靶向作用和在体内肿瘤中的有效积累。此外,该平台用于癌症治疗的潜在应用被探索为石蒜素-I-缀合的金纳米棒(LGNRs)。LGNRs在近红外(NIR,808 nm)照射下表现出选择性的胞内转运和高效的光热效应,在体内外均能有效杀伤癌细胞。因此,已建立的LGNPs和LGNRs在肿瘤靶向给药和光热治疗方面具有巨大的潜力。
Cell penetrating peptides (CPPs) are commonly utilized for intracellular delivery of functional materials to circumvent biomembrane barrier. However, further application of CPPs is hindered by lacking selectivity toward targeted cells. The spider venom peptide, lycosin-I, is a CPP with potent cytotoxicity to cancer cells, which might enable lycosin-I to deliver functional materials into cancer cells selectively. In this study, we demonstrated that the lycosin-I-conjugated spherical gold nanoparticles (LGNPs) not only exhibited efficient cellular internalization efficiency toward cancer cells but also displayed unprecedented selectivity over noncancerous cells. Although LGNPs were removed from the living circulatory system via reticuloendothelial system-dominant clearance modes without noticeable adverse effects to animals, they actually displayed active tumor-targeting effects and efficient accumulation in tumors in vivo. Furthermore, the potential application of this platform for cancer therapy was explored by lycosin-I-conjugated gold nanorods (LGNRs). LGNRs exhibited selective intracellular translocation towards cancer cells and efficient photothermal effect under near infrared (NIR, 808 nm) irradiation, which consequently killed cancer cells in vitro and in vivo effectively. Therefore, the established LGNPs and LGNRs possessed great potential in cancer-targeting delivery and photothermal therapy.
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