The antitumor effect of cisplatin-loaded thermosensitive chitosan hydrogel combined with radiotherapy on nasopharyngeal carcinoma

摘要

Cisplatin-based chemo-radiotherapy (RT) is the most effective treatment in patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). However, traditional chemotherapy drugs have low bioavailability and targeting ability, which reduce their antitumor effects. Therefore, we developed a chitosan/ cis-dichlorodiamineplatinum (CS/DDP) hydrogel-based drug delivery system for the in situ treatment of NPC in combination with RT, and investigated their synergistic antitumor efficacy and underlying mechanism of action. CS/DDP hydrogel remarkably prolonged the survival time (81 days) when combined with RT compared to the control group (P 0.01). The main mechanism was likely the increase in cancer cell apoptosis (76.23 +/- 1.13%, p 0.01). Furthermore, the CS/DDP hydrogel in combination with RT also increased X-rayinduced DSBs and gamma-H2AX foci, induced G2/M phase arrest, inhibited cell proliferation by blocking Ki-67, and decreased CD31 + micro-vessel density (MVD). These results underscore the therapeutic potential of the combination of CS/DDP hydrogel and RT for localized NPC.