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

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 LuXiaoyuan Chen

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The success of radiotherapy relies on tumor-specific delivery of radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties by changing only the introduced bissilylated organosilica precursors. The biodegradable thioether-hybridized HMONs are chosen for efficient co-delivery of tert-butyl hydroperoxide (TBHP) and iron pentacarbonyl (Fe(CO)5). Distinct from conventional RT, radiodynamic therapy (RDT) is developed by taking advantage of X-ray-activated peroxy bond cleavage within TBHP to generate •OH, which can further attack Fe(CO)5 to release CO molecules for gas therapy. Detailed in vitro and in vivo studies reveal the X-ray-activated cascaded release of •OH and CO molecules from TBHP/Fe(CO)5 co-loaded PEGylated HMONs without reliance on oxygen, which brings about remarkable destructive effects against both normoxic and hypoxic cancers.
Original languageEnglish (US)
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Mar 18 2019

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