联合中子流外照射的具有肿瘤代谢靶向的载药纤维毡及其抗癌研究

A novel "pincer attack" strategy, which uniting the surgical therapy, chemotherapy and radiotherapy, was proposed to confront the war on liver cancer, which known as the king of cancer. This was the first time to revisited the war on cancer from the aspect of tactics. The strategy was carrying out by combination of the DCA loaded electrospun mats targeting the energy metabolism with the neutron ray killing the hypoxic cancer cell specificity. This strategy contained two different parts, one is on the layer of the action mode, the other is on the point of the action time. The action mode means that DCA switched off the energy supply of the cancer cell by the effect of energy metabolism targeting, and this effect can act as radiosensitizer, which magnified the cancer cell killing ability of the neutron. The action time means that there was a delay of the malignant proliferation of the tumor cells, which can gain the action time of anti-cancer drugs to be controlled release from the electrospun mats and diffused into the tumor. So this is the first time to present the novel method of neutron external exposure, guiding by the energy matbolism target of cancer cell form the DCA loaded electrospun mats.This integrity strategy would realize the superiority of the three traditonal approachs relatively complemented, making it easy to achieve a better therapeutic effect for cancer therapy and avoid side-effects when high-dose of DCA and neutron used.

本项目首次从战术角度提出了一套"前后夹击"的抗癌策略来实现手术治疗、化疗与放疗这三大传统抗癌手段的强强联合，从而应对具有"癌症之王"之称的肝癌的抗癌之战。具有能量代谢靶向的二氯乙酸盐抗癌纤维毡和具有对乏氧癌细胞特异性杀伤的中子流照射的技术被选择从两个不同层次来贯彻这套"前后夹击"的抗癌策略：一方面是二氯乙酸盐对癌细胞的能量代谢靶向可以特异性地切断其恶性增殖的能量供给，从而使癌细胞对中子流照射更敏感，实现从作用方式上的"前后夹击"效果；二是中子流放疗的作用深度的优势可以很好地抑制肿瘤细胞的恶性增殖的步伐，从而为从纤维毡释放的药物扩散至目标癌细胞赢取充分的时间，实现最后合兵一处的"前后夹击"的效果。本课题第一次提出了一套通过二氯乙酸盐纤维毡剂型的代谢靶向制导中子射线的中子流外照射抗癌手段。这套整体施治策略实现了三大传统手段的优势互补，在保证抗癌疗效的同时，极大地降低机体的系统毒性。

本研究利用具有能量代谢靶向的二氯乙酸盐抗癌纤维毡和具有对乏氧癌细胞特异性杀伤的中子流照射的技术形成“前后夹击”的抗癌策略。其一，二氯乙酸盐能够逆转癌细胞的能量代谢方式，特异性的切断恶性肿瘤的能量供应，进而使癌细胞对于中子流照射更为敏感。其二，中子流放疗的优势是能够很好地抑制肿瘤细胞的恶性增殖的步伐，为从纤维毡释放的药物扩散至目标癌细胞赢取充分的时间。二者协同作用，实现“前后夹击”效果。采用含有二氯乙酸盐抗癌纤维毡，结合中子流照射，从细胞水平和活体水平评价了联合治疗的有效性。系统全面的研究了各种药物载药抗癌纤维毡在联合中子流照射的策略下的针对细胞和肝癌及原位瘤动物模型下的抗癌活性和机制的差异。同时探索了中子俘获治疗肿瘤。. 本项目为建立一系类有效、简便、毒副作用小的抗癌路径奠定了重要的实验和理论基础。