Peptide-containing aggregates as selective nanocarriers for therapeutics
Peptide-containing aggregates as selective nanocarriers for therapeutics
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DOI：
10.1002/cmdc.200700269
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发表时间：
2008-04-01
期刊：
影响因子：
3.4
通讯作者：
Morelli, Giancarlo
中科院分区：
文献类型：
--
作者：
Accardo, Antonella;Tesauro, Diego;Morelli, Giancarlo
新的非载体是通过组装两个两亲性单体获得的：一个含有生物活性肽CCK8，由多分散聚乙二醇隔开，从两个疏水尾部（(C18)2PEG2000CCK8），另一个含有螯合剂，能够提供稳定的放射性标记的配合物，连接到一些疏水部分（(C18)2DTPAGlu）。利用动态光散射、小角中子散射和低温透射电镜对超分子聚集体的大小和形状进行了结构表征。在我们研究的实验条件下（pH为7.4，单体的摩尔比为30:70），存在高度多分散的聚集体：棒状胶束，半径约为40埃，长度约为700埃，开放的双层碎片，厚度约为65埃，可能还有囊泡。生物活性肽暴露在聚集体的外表面，使得纳米载体可以选择性地靶向癌细胞过度表达的胆囊收缩素受体。本文报道了铟-111在核医学实验中的体外结合试验和体内生物分布研究。此外，通过使用细胞毒性药物阿霉素，报道了有关聚集体的载药能力及其对靶细胞的药物效率的初步数据。受体阳性细胞和对照细胞与充满阿霉素的含肽聚集体的孵育表明，对于在阿霉素存在下孵育的样本，受体表达细胞的细胞存活率明显低于对照。
New nonocarriers ore obtained by assembling two amphiphilic monomers: one containing the bioactive peptide CCK8 spaced, by a polydisperse poly(ethylene glycol), from two hydrophobic tails ((C18)2PEG2000CCK8), and the other containing a chelating agent able to give stable radiolabeled indium-117 complexes linked to the some hydrophobic moiety ((C18)2DTPAGlu). The size and shape of the supramolecular aggregates were structurally characterized by dynamic light scattering, small-angle neutron scattering, and cryogenic transmission electronic microscopy. Under the experimental conditions we investigated (pH 7.4 and molar ratio between monomers 30:70), there is the presence of high polydisperse aggregates: rod-like micelles with a radius of similar to 40 angstrom and length >700 angstrom, open bilayer fragments with thickness similar to 65 angstrom, and probably vesicles. The presence of the bioactive peptide well exposed on the external surface of the aggregate allows selective targeting of nanocarriers towards the cholecystokinin receptors overexpressed by the cancerous cells. In vitro binding assays and in vivo biodistribution studies by nuclear medicine experiments using indium-111 are reported. Moreover, preliminary data concerning the drug loading capability of the aggregates and their drug efficiency on the target cells is reported by using the cytotoxic drug doxorubicin. Incubation of receptor-positive and control cells with peptide-containing aggregates filled with doxorubicin shows significantly lower cell survival in receptor-expressing cells relative to the control, for samples incubated in the presence of doxorubicin.