Self-Assembling Peptide Amphiphile-Based Nanofiber Gel for Bioresponsive Cisplatin Delivery

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.This project was partially supported by Grant No. P20RR021929 from the National Center for Research Resources (NIH/NCRR). This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2007-357-E0041). This work was partially supported by the UAB BERM Center Pilot Grant (H.-W.J.) and T32EB004312 from the NIBIB (J.A.)