Department of Neurosurgery, The Affiliated Brain Hospital With Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, 210029, China.
Department of Neuro-Psychiatric Institute, The Affiliated Brain Hospital With Nanjing Medical University, Nanjing, 210029, China.
J Nanobiotechnology. 2023 Jul 5;21(1):210. doi: 10.1186/s12951-023-01960-w.
Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.
尽管 RNA 干扰 (RNAi) 疗法已成为癌症治疗的一种有潜力的工具，但 RNAi 在胶质母细胞瘤 (GBM) 中的应用仍然存在障碍。在此，为了提高 RNAi 对 GBM 的治疗效果，开发了一种癌细胞膜 (CCM)伪装的缺氧触发 RNAi 纳米药物，用于递送小干扰 RNA (siRNA)，以增强细胞对化疗和放疗的敏感性。我们合成的 CCM 伪装的 RNAi 纳米药物通过同型识别表现出延长的血液循环、高血脑屏障 (BBB) 转胞吞作用和在 GBM 部位的特异性积累。在缺氧区域触发了破坏和有效的抗 GBM 作用，通过沉默磷酸甘油酸激酶 1 (PGK1) 来增强紫杉醇诱导的化疗，并使缺氧 GBM 细胞对电离辐射敏感，从而有效地抑制肿瘤。总之，已经开发出一种仿生智能 RNAi 纳米药物用于 siRNA 递送来协同介导联合化疗/放疗，具有无免疫和缺氧触发特性，为原位 GBM 治疗提供了高存活率。
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