Generic synthesis of small-sized hollow mesoporous organosilica nanoparticles for oxygen-independent X-ray-activated synergistic therapy

• DOI: 10.1038/s41467-019-09158-1
• Publication Date: 2019-03-19T18:45:35Z
• Authors: Wenpei Fan; Nan Lu; Zheyu Shen; Wei Tang; Bo Shen; Zhaowen Cui; Lingling Shan; Zhen Yang; Zhantong Wang; Orit Jacobson; Zijian Zhou; Yijing Liu; Ping Hu; Weijing Yang; Jibin Song; Yang Zhang; Liwen Zhang; Niveen M. Khashab; Maria A. Aronova; Guangming Lu; Xiaoyuan Chen
• Keywords: Iron pentacarbonyl; Mesoporous organosilica; Tumor Hypoxia

The success of radiotherapy relies on tumor-specific delivery radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis a library small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization diverse organic moieties by changing only introduced bissilylated precursors. biodegradable thioether-hybridized HMONs are chosen efficient co-delivery tert-butyl hydroperoxide (TBHP) iron pentacarbonyl (Fe(CO)5). Distinct from conventional RT, radiodynamic therapy (RDT) is developed taking advantage X-ray-activated peroxy bond cleavage within TBHP generate •OH, which can further attack Fe(CO)5 release CO molecules gas therapy. Detailed in vitro vivo studies reveal cascaded •OH TBHP/Fe(CO)5 co-loaded PEGylated without reliance oxygen, brings about remarkable destructive effects against both normoxic hypoxic cancers.