期刊
MOLECULAR PHARMACEUTICS
卷 6, 期 3, 页码 978-985出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp900009n
关键词
Cisplatin; matrix metalloproteinase-2; nanofiber; peptide amphiphile; targeted drug delivery
资金
- National Center for Research Resources (NIH/NCRR) [P20RR021929]
- Korean Government (MOEHRD) [KRF-2007-357-E0041]
- UAB BERM Center
- NIBIB [T32EB004312]
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 degrees 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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