Anti-Tumor Effect of Controlled Drug Delivery Figure 4. Systematic toxicity in the SAHA-DDP/PECE treated mice. H&E staining of section of major tissues obtained from tumor beard mice which received two doses of NS, PECE, SAHA, DDP, SAHA-DDP and SAHA-DDP/PECE. Heart, liver, spleen, lung and kidney were harvested at day 28 after intravenous injection. (A) Mean body weights on days 7, 10, 13, 16, 19, 22, 25 and 28 of mice treated with two doses of NS, PECE, SAHA, DDP, SAHA-DDP and SAHA-DDP/PECE; error bars correspond to 95% confidence intervals, Values are means6SD (n = 10 mice per group). doi:10.1371/journal.pone.0033860.g004 vivo at body temperature about 37uC [41,42]. The previous results strongly support that PECE hydrogel can endue the delayedrelease properties and increased permeability of drugs. For intratumoral chemotherapy, prolonged stay and increased permeability of drugs are helpful for better disease control. In fact, the SAHA-DDP/ PECE hydrogel system did show significantly increased therapeutic effects for OSCC. SAHA-DDP/PECE hydrogel system with direct intratumoral injections may be a useful method in treatment for oral cancer and other solid tumors. Figure 5. SAHA-DDP/PECE inhibited cell proliferation and intratumoral angiogenesis in vivo. (A) PCNA-positive cells were rich in NS and PECE groups. Whereas, the percentage of PCNA-positive cells in SAHA, DDP, SAHA-DDP and SAHA-DDP/PECE groups were significantly decreased in turn (*P,0.05). (magnification, 6200) (B) Angiogenesis within tumors was detected by CD34 staining of micro vessels. The average number of micro vessels per vascular hot spot was significantly decreased in SAHA-DDP/PECE treated tissues compared with those in the three control groups (*P,0.05). doi:10.1371/journal.pone.0033860.g005 PLoS ONE | www.plosone.org 6 April 2012 | Volume 7 | Issue 4 | e33860