Self-assembling peptide amphiphile-based nanofiber gel for bioresponsive cisplatin delivery.

Self-assembling peptide amphiphile-based nanofiber gel for bioresponsive cisplatin delivery.
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DOI:
10.1021/mp900009n
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发表时间:
2009-05
影响因子:
4.9
通讯作者:
Jo S
Jo S
中科院分区:
医学2区
文献类型:
--
作者:
Kim JK;Anderson J;Jun HW;Repka MA;Jo S

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本研究的目的是开发一种具有自组装肽两亲物 (PA) 的生物响应性顺铂 (CDDP) 递送系统,该系统包含细胞粘附基质金属蛋白酶 2 (MMP-2) 敏感的 GTAGLIGQRGDS 和脂肪酸。 CDDP 和 PA 的混合物在 37 °C 下孵育 5 小时后,自发形成仿生 CDDP-PA 凝胶。通过流变学分析证实CDDP-PA凝胶形成。通过透射电子显微镜 (TEM) 确定凝胶内自组装 CDDP-PA 纳米纤维的结构。体外 MMP-2 触发的 CDDP 释放证明了仿生凝胶的生物响应性药物释放。 MMP-2 敏感的 CDDP 释放取决于培养基中的酶浓度。通过在含有 MMP-2 的介质中降解的凝胶的 TEM 图像证实了 CDDP-PA 凝胶的酶促降解。 MMP-2触发的CDDP释放以及凝胶中RGDS的呈现可能为靶向抗癌药物递送提供空间和时间控制的递送系统。
The aim of this study is to develop a bioresponsive cisplatin (CDDP) delivery system with a self-assembling peptide amphiphile (PA) comprising a cell-adhesive matrix metalloproteinase-2 (MMP-2)-sensitive GTAGLIGQRGDS and a fatty acid. A biomimetic CDDP-PA gel was spontaneously formed upon incubating a mixture of CDDP and the PA for 5 h at 37 °C. CDDP-PA gel formation was confirmed by rheological analysis. The structure of self-assembled CDDP-PA nanofibers inside the gel was determined by transmission electron microscopy (TEM). Bioresponsive drug release from the biomimetic gel was demonstrated by in vitro MMP-2-triggered CDDP release. The MMP-2-sensitive CDDP release was dependent on the enzyme concentration in the medium. Enzymatic degradation of the CDDP-PA gel was confirmed by TEM images of the gel degraded in an MMP-2 containing medium. The MMP-2-triggered CDDP release as well as the presentation of RGDS in the gel would potentially provide a spatially and temporally controlled delivery system for targeted anticancer drug delivery.
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