Tailoring Silica-Based Nanoscintillators for Peroxynitrite-Potentiated Nitrosative Stress in Postoperative Radiotherapy of Colon Cancer

摘要

The development of a manageable reactive nitrogen species-potentiated nitrosative stress induction system for cancer therapy has remained elusive. Herein, tailored silica-based nanoscintillators were reported for low-dosage X-ray boosting for the in situ formation of highly cytotoxic peroxynitrite (ONOO-). Significantly, cellular nitrosative stress revolving around the intracellular protein tyrosine nitration through ONOO- pathways was explored. High-energy X-rays were directly deposited on silicabased nanoscintillators, forming the concept of an open source and a reduced expenditure-aggravated DNA damage strategy. Moreover, the resultant ONOO-, along with the released nitric oxide, not only can act as "oxygen suppliers" to combat tumor hypoxia but also can induce mitochondrial damage to initiate caspasemediated apoptosis, further improving the therapeutic efficacy of radiotherapy. Thus, the design of advanced nanoscintillators with specific enhanced nitrosative stress offers promising potential for postoperative radiotherapy of colon cancer.

关键词