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 Lu () and Xiaoyuan Chen ()
Additional contact information
Wenpei Fan: National Institutes of Health
Nan Lu: Zhejiang University School of Medicine
Zheyu Shen: National Institutes of Health
Wei Tang: National Institutes of Health
Bo Shen: Fudan University
Zhaowen Cui: Chinese Academy of Sciences
Lingling Shan: National Institutes of Health
Zhen Yang: National Institutes of Health
Zhantong Wang: National Institutes of Health
Orit Jacobson: National Institutes of Health
Zijian Zhou: National Institutes of Health
Yijing Liu: National Institutes of Health
Ping Hu: Chinese Academy of Sciences
Weijing Yang: National Institutes of Health
Jibin Song: National Institutes of Health
Yang Zhang: King Abdullah University of Science and Technology
Liwen Zhang: King Abdullah University of Science and Technology
Niveen M. Khashab: King Abdullah University of Science and Technology
Maria A. Aronova: National Institutes of Health
Guangming Lu: Jinling Hospital, Medical School of Nanjing University
Xiaoyuan Chen: National Institutes of Health

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09158-1

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