Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma

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.

Automated summary

In order to overcome the challenges of using RNA interference (RNAi) therapy for glioblastoma (GBM), researchers developed a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine for siRNA delivery. This nanomedicine showed prolonged blood circulation, efficient blood-brain barrier transcytosis, and specific accumulation in GBM sites. By silencing the PGK1 gene and enhancing the effects of paclitaxel-induced chemotherapy and ionizing radiation, this RNAi nanomedicine effectively suppressed tumors in hypoxic regions. In summary, a biomimetic intelligent RNAi nanomedicine was developed to deliver siRNA and synergistically mediate combined chemo/radiotherapy for orthotopic GBM treatment.