新型纳米药物-温敏型水凝胶复合药物传输载体同时提高术后腹腔化疗效果和防治术后粘连的机理研究

Cancer, one of the major diseases, is a serious hazard to public health. Cytoreductive surgery is an effective method for patients with advanced cancers such as ovarian or other abdominopelvic malignancies, which could create favorable conditions for postoperative chemotherapy. However, residual tumors and severe peritoneal adhesions are the two major concerns after cytoreductive surgery, which have great impact on prognosis of patients. In the present project, we aim to synthesize a novel non-toxic and in vivo-degradation-time-controlled thermosensitive hydrogel. Honokiol and cisplatin were first incorporated into polymeric micelles by nanotechnology. Subsequently, the drugs incorporated micelles were loaded into thermosensitive hydrogel to form the novel "nanomedicine-hydrogel composite", which combined drug delivery system for tumor local chemotherapy and anti-adhesion barrier. Therapeutic effect and mechanism of "nanomedicine-hydrogel composite" in improving intraperitoneal chemotherapeutic effect and preventing postsurgical adhesion formation simultaneously after cytoreductive surgery were investigated in detail. In this study, we will establish platform technologies for preparation of injectable, biodegradable, and in vivo-degradation-time-controlled thermosensitive hydrogel, and for improving water solubility of hydrophobic drugs by nanotechnology. Furthermore, a novel drug formulation will be developed for improving intraperitoneal chemotherapy effect of ovarian peritoneal carcinomatosis and preventing postsurgical adhesion formation simultaneously, which provided a theoretical basis for synchronous treatment of anti-tumor and anti-adhesion after cytoreductive surgery.

癌症是当前严重危害人类健康的重大疾病之一。对于卵巢癌和其他晚期盆腹腔恶性肿瘤，肿瘤细胞减灭术是一种非常有效的治疗方法，可以为术后化疗创造有利条件。但肿瘤细胞减术后肿瘤残留和严重的盆腹腔粘连对患者预后造成很大影响。本项目拟在前期工作基础上，合成出新型无毒的、体内降解时间可控的温度敏感型水凝胶。先将和厚朴酚和顺铂装载于纳米胶束中，然后将载药胶束装载于水凝胶中，将水凝胶的药物缓释作用和防粘连阻隔作用相结合，制备出新型"纳米药物-水凝胶"复合药物传输载体，达到在术后同时提高腹腔化疗效果和防治腹腔粘连的双重功效，并研究其作用机理。通过本研究将建立制备新型局部治疗用可注射、体内降解时间可控的温度敏感型水凝胶的平台技术和通过纳米技术提高难溶性药物水溶性的平台技术；将构建一种有效治疗腹腔转移卵巢癌和预防术后粘连的药物新剂型，为肿瘤细胞减灭术后抗癌防粘同步治疗模式提供了理论依据。

癌症是当前严重危害人类健康的重大疾病之一。对于卵巢癌和其他晚期盆腹腔恶性肿瘤，肿瘤细胞减灭术是一种非常有效的治疗方法，可以为术后化疗创造有利条件。但肿瘤细胞减术后肿瘤残留和严重的盆腹腔粘连对患者预后造成很大影响。本项目拟在前期工作基础上，合成出新型无毒的、体内降解时间可控的温度敏感型水凝胶。先将抗肿瘤药物装载于纳米胶束中，然后将载药胶束装载于水凝胶中，将水凝胶的药物缓释作用和防粘连阻隔作用相结合，制备出新型“纳米药物-水凝胶”复合药物传输载体，达到在术后同时提高腹腔化疗效果和防治腹腔粘连的双重功效，并研究其作用机理。通过本研究将建立制备新型局部治疗用可注射、体内降解时间可控的温度敏感型水凝胶的平台技术和通过纳米技术提高难溶性药物水溶性的平台技术；将构建一种有效治疗腹腔转移卵巢癌和预防术后粘连的药物新剂型，为肿瘤细胞减灭术后抗癌防粘同步治疗模式提供了理论依据。本项目进展顺利，已经完成了纳米药物制备，纳米药物-水凝胶复合物制备，体外性能研究，体内同时提高腹腔化疗效果和防治腹腔粘连的疗效和机理研究。目前已经发表SCI论文15篇（全部论文IF均大于3），其中11篇IF大于5。项目负责人入选国家“万人计划”青年拔尖人才。