Anti-Tumor Effect of Controlled Drug Delivery Figure 6. SAHA-DDP/PECE induced apoptosis in vivo. (A) Induction of apoptosis was indicated by TUNEL assay. The TUNEL-positive cells display dark green nuclei and are observed under a fluorescence microgroup (6400 magnification). TUNEL-positive nuclei were significantly increased in SAHA-DDP/PECE treated tissues compared with those in the control groups (*P,0.05). (B) Detection of caspase-3, Caspase-8 and Caspase-9 by Western blots. GAPDH was used as equal loading control. doi:10.1371/journal.pone.0033860.g006 We then investigated the possible application of this drug delivery system for the treatment of experimental OSCC by administrating the DDP and SAHA loaded PECE hydrogel peritumorally of OSCC-bearing mice. Our experimental results demonstrated that such a strategy as this allows the carrier system to show a sustained release of DDP and SAHA in vivo as well as improved therapeutic effects compared with a simple additive therapeutic effect of SAHA-DDP on murine OSCC. Furthermore, peritumorally administration of the SAHA-DDP/PECE was well tolerated and showed with no observable toxicity. In conclusion, our data showed that intratumoral delivery of SAHA-DDP/PECE system was an efficient way to transfer PLoS ONE | www.plosone.org 7 April 2012 | Volume 7 | Issue 4 | e33860