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-ray-induced DSBs and γ-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.
Keywords: Chitosan; Cisplatin; Nasopharyngeal carcinoma; Radiotherapy; Thermosensitive hydrogel.
Copyright © 2018. Published by Elsevier B.V.