Yang Yuan, Du Ting, Zhang Jiumeng, Kang Tianyi, Luo Li, Tao Jie, Gou Zhiyuan, Chen Shaochen, Du Yanan, He Jiankang, Jiang Shu, Mao Qing, Gou Maling
State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu P. R. China.
Department of Neurosurgery West China Hospital Sichuan University Chengdu P. R. China.
Adv Sci (Weinh). 2017 Mar 30;4(8):1600491. doi: 10.1002/advs.201600491. eCollection 2017 Aug.
Gene therapy has great promise for glioblastoma treatment; however, it remains a great challenge to efficiently deliver genes to the brain. The incomplete resection of glioblastoma always leads to poor prognosis. Here, a 3D-engineered conformal implant for eradicating the postsurgery residual glioblastoma is designed. This implant is constructed by 3D-printing technology to match the tumor cavity and release an oncolytic virus-inspired DNA nanocomplex to kill glioblastoma cells through apoptosis induction. Meanwhile, a 3D-engineered subcutaneous glioblastoma xenograft is built to mimic the resection tumor cavity in mice. Insertion of the implant into the glioblastoma resection cavity efficiently delays tumor recurrence and significantly prolongs overall survival. This study provides a proof-of-concept of glioblastoma therapy using a conformal implant that releases oncolytic DNA nanocomplexs. This strategy can lead to the development of future precision therapy for eradicating postsurgery residual tumors.
基因治疗在胶质母细胞瘤治疗方面具有巨大潜力;然而,将基因有效递送至大脑仍然是一项巨大挑战。胶质母细胞瘤的不完全切除总是导致预后不良。在此,设计了一种用于根除术后残留胶质母细胞瘤的三维工程化适形植入物。该植入物通过3D打印技术构建,以匹配肿瘤腔,并释放一种受溶瘤病毒启发的DNA纳米复合物,通过诱导凋亡来杀死胶质母细胞瘤细胞。同时,构建了一种三维工程化皮下胶质母细胞瘤异种移植模型,以模拟小鼠体内的切除肿瘤腔。将植入物插入胶质母细胞瘤切除腔可有效延迟肿瘤复发并显著延长总生存期。本研究提供了使用释放溶瘤DNA纳米复合物的适形植入物治疗胶质母细胞瘤的概念验证。该策略可引领未来根除术后残留肿瘤的精准治疗的发展。