Journal
ACS NANO
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.3c00269
Keywords
mesoporous silica; radiation resistance; hypoxia-responsive; glioblastoma; siRNA therapy
Ask authors/readers for more resources
In this study, a biodegradable selenium-engineered mesoporous silica nano-capsule was developed for at-site RNA interference to inhibit the invasive growth of radiotherapy-resistant glioblastoma (rrGBM) and achieve maximum therapeutic benefit. The nanocapsule showed high stability, efficient blood-brain barrier penetration, and potent accumulation in rrGBM. It effectively reduced tumor growth and invasion, prolonging survival in an rrGBM model.
Radiotherapy-resistant glioblastoma (rrGBM) remains a significant clinical challenge because of high infiltrative growth characterized by activation of antiapoptotic signal transduction. Herein, we describe an efficiently biodegradable selenium-engineered mesoporous silica nano-capsule, initiated by high-energy X-ray irradiation and employed for at-site RNA interference (RNAi) to inhibit rrGBM invasion and achieve maximum therapeutic benefit. Our radiation-triggered RNAi nanocapsule showed high physiological stability, good blood-brain barrier transcytosis, and potent rrGBM accumulation. An intratumoral RNAi nanocapsule permitted low-dose X-ray radiation-triggered dissociation for cofilin-1 knockdown, inhibiting rrGBM infiltration. More importantly, tumor suppression was further amplified by electron-affinity aminoimidazole products converted from metronidazole polymers under X-ray radiation-exacerbated hypoxia, which sensitized cell apoptosis to ionizing radiation by fixing reactive oxygen species-induced DNA lesions. In vivo experiments confirmed that our RNAi nanocapsule reduced tumor growth and invasion, prolonging survival in an orthotopic rrGBM model. Generally, we present a promising radiosensitizer that would effectively improve rrGBM-patient outcomes with low-dose X-ray irradiation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available