Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, 310000, Hangzhou, Zhejiang, China.
Nat Commun. 2019 Mar 18;10(1):1241. doi: 10.1038/s41467-019-09158-1.
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)). 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) 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) co-loaded PEGylated HMONs without reliance on oxygen, which brings about remarkable destructive effects against both normoxic and hypoxic cancers.
放射治疗的成功依赖于肿瘤特异性递送来减弱缺氧抵抗。在这里，我们报告了一种氨辅助热水刻蚀策略，用于通用合成具有单、双、三甚至四元骨架杂交的各种有机基团的小型（亚 50nm）中空介孔有机硅纳米粒子（HMONs）库，只需改变引入的双硅烷基有机硅前体。选择可生物降解的硫醚杂交 HMONs 来高效共递送叔丁基过氧化氢（TBHP）和五羰基铁（Fe(CO)）。与传统的 RT 不同，放射动力学治疗（RDT）是通过利用 X 射线激活 TBHP 中的过氧键裂解生成•OH 来开发的，•OH 可以进一步攻击 Fe(CO)释放 CO 分子进行气体治疗。详细的体外和体内研究揭示了 TBHP/Fe(CO)共载 PEG 化 HMONs 中•OH 和 CO 分子的 X 射线激活级联释放，不依赖于氧气，这对常氧和缺氧癌症都带来了显著的破坏作用。
