抗瘤多肽自组装纳米材料RADA-KP10/卡莫司汀缓释体系治疗恶性胶质瘤的研究

Malignant gliomas are the most common primary brain tumors. Postoperative residual tumor is often the main cause of tumor recurrence. Recent studies have demonstrated the utility of scaffolds carrying chemotherapy drugs in residual cavity could improve the prognosis the prolong the survival time. In this project, based on previous research on peptide self-assembling nanofibers, we design and synthesis a novel self-assembling peptide RADA-KP10 containing a decapeptide kisspeptin-10 (KP-10) derived from the primary translation product of KiSS1 gene, then we build a RADA-KP10/carmustine slow-release system. In this system, RADA-KP10 self-assembling scaffold could suppress angiogenesis, inhibit proliferation and induce apoptosis of cancer cells. Meanwhile, it could delivery and controlled-release carmustine. The RADA-KP10/carmustine slow-release system could be injected into the resection cavity of malignant gliomas. In vivo, RADA-KP10 scaffold can be attached conformally entirely to the surface of cavity and have synergistic effect with carmustine on reducing the recurrence of gliomas and prolonging the life time. This project treats malignant gliomas comprehensively from different aspects, presents a new way of the treatment of malignant gliomas, provides some new ideas for the adjunct therapy after surgery of solid tumors, and has important scientific significance and broad application foreground.

恶性胶质瘤是最常见的原发脑肿瘤，术后肿瘤残留往往是肿瘤复发的根源。研究证实，将负载化疗药物的生物材料植入至术后残腔，可以改善预后，延长生存时间。 本项目以前期多肽自组装纳米材料的研究为基础，选用肿瘤转移抑制基因KiSS1编码的十肽Kisspeptin-10为活性片段，设计合成具有自主知识产权的抗瘤多肽自组装分子RADA-KP10，构建RADA-KP10/卡莫司汀自组装材料缓释体系；该体系中RADA-KP10可抑制血管生成、肿瘤细胞增殖和促进肿瘤细胞凋亡，同时携载并缓慢释放卡莫司汀；将RADA-KP10/卡莫司汀缓释体系注射植入恶性胶质瘤术后残腔中，活性多肽材料可完全适形帖附在残腔表面，与卡莫司汀两者发挥协同作用，减少恶性胶质瘤术后复发，延长生存时间。此设计从多角度综合治疗恶性胶质瘤，为胶质瘤的治疗开辟新的途径，为各种实体瘤术后辅助治疗提供新的思路，具有重要的科学意义和广泛的应用前景。

恶性胶质瘤是最常见的原发脑肿瘤，术后肿瘤残留往往是肿瘤复发的根源。研究证实，将负载化疗药物的生物材料植入至术后残腔，可以改善预后，延长生存时间。.本项目以前期多肽自组装材料的研究为基础，设计合成含有蜂毒肽的自组装多肽分子RADA-melittin，构建RADA-melittin/吲哚菁绿(ICG)自组装材料缓释体系MRI；该体系中RADA-melittin可携载并缓慢释放ICG，两者可协同抑制胶质瘤C6细胞增殖和促进肿瘤细胞凋亡，同时；将MRI体系注射植入恶性胶质瘤中，联合ICG光动力效应，抑制肿瘤生长。此设计从多角度综合治疗恶性胶质瘤，为胶质瘤的治疗开辟新的途径，为各种实体瘤术后辅助治疗提供新的思路，具有重要的科学意义和广泛的应用前景。