Doxorubicin-triggered self-assembly of native amphiphilic peptides into spherical nanoparticles.
Doxorubicin-triggered self-assembly of native amphiphilic peptides into spherical nanoparticles.
复制标题
阿霉素触发天然两亲肽自组装成球形纳米颗粒
DOI：
10.18632/oncotarget.11213
复制
发表时间：
2016-09-06
期刊：
影响因子：
--
通讯作者：
Wu G
中科院分区：
文献类型：
--
作者：
Fan X;Zhao F;Wang X;Wu G
在这项研究中，我们设计并制造了自组装纳米球，它由 P45 肽和阿霉素 (Dox) 组成。 P45 是一种杂合肽，由通过丝氨酸接头与人 matrilin-1 C 末端结构域连接的 Arg-Gly-Asp 基序组成。制备的纳米球具有均匀的桑葚球形形状，直径为63 nm，具有良好的多分散性和较高的Dox载药效率。在 RGD 基序存在的情况下，Dox/P45 纳米球可以特异性靶向具有高整合素 αvβ3 表达的 A549 细胞。共聚焦激光扫描显微镜和流式细胞术结果显示细胞对 Dox/P45 的摄取增强，CCK8 测定表明纳米球对正常人胚胎肾 293 细胞的细胞毒性较低。此外，制造的纳米球在生理环境中稳定，但它们在酸性气氛中分解并表现出快速的 Dox 释放，从而在细胞摄取后以特定的 pH 敏感释放到细胞质中。这些结果表明，天然两亲性肽可以用作纳米药物的载体，用于靶向递送以及癌症治疗的受控药物释放。
In this study, we designed and fabricated self-assembly nanospheres, which consisted of a P45 peptide and doxorubicin (Dox). P45 is a hybrid peptide composed of an Arg-Gly-Asp motif linked to the human matrilin-1 C-terminal domain by a serine linker. The fabricated nanospheres had a uniform mulberry-like spherical shape, a diameter of 63 nm, excellent polydispersity, and high Dox drug-loading efficiency. In the presence of the RGD motif, the Dox/P45 nanospheres could specifically target A549 cells, which have high integrin αvβ3 expression. Confocal laser scanning microscopy and flow cytometry results showed the enhanced cellular uptake of Dox/P45, and the CCK8 assay indicated the low cytotoxicity of the nanospheres to normal human embryonic kidney 293 cells. Furthermore, the fabricated nanospheres were stable in a physiological environment, but they disassembled and exhibited a rapid Dox release in an acidic atmosphere, allowing for a specific pH-sensitive release into cytosol after cellular uptake. These results suggest that natural amphiphilic peptides can be used as carriers of nanodrugs for targeting delivery as well as controlled drug release for cancer therapy.