A Biomimetic Nanogenerator of Reactive Nitrogen SpeciesBased on Battlefield Transfer Strategy for EnhancedImmunotherapy.

【作者】 Feng, Qianhua;Li Yuzhen; Wang Ning;Hao Yutong;Chang Junbiao;Wang Zeying;Zhang Xueli;Zhang Zhenzhong;Wang Lei.

【期刊名】 Small

【影响因子】 2020年:10.856

【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2020, 2002138

【关键词】 biomimetic, hemoglobin, immunotherapy, nitrite reductase activity,reactive nitrogen species

【摘要】Currently, cell membrane is always utilized for the construction of biomimeticnanoparticles. By contrast, mimicking the intracellular activity seems moremeaningful. Inspired by the specific killing mechanism of deoxy-hemoglobin(Hb) dependent drug (RRx-001) in hypoxic red blood cells (RBC), this workaims to develop an inner and outer RBC-biomimetic antitumor nanoplatformthat replicates both membrane surface properties and intracellularly certaintherapeutic mechanisms of RRx-001 in hypoxic RBC. Herein, RRx-001 andHb are introduced into RBC membrane camouflaged TiO2 nanoparticles.Upon arrival at hypoxic tumor microenvironment (TME), the biomimeticnanoplatform (R@HTR) is activated and triggers a series of reactions togenerate reactive nitrogen species (RNS). More importantly, the potentantitumor immunity and immunomodulatory function of RNS in TME aredemonstrated. Such an idea would transfer the battlefield of RRx-001 fromhypoxic RBC to hypoxic TME, enhancing its combat capability. As a proofof concept, this biomimetic nanoreactor of RNS exhibits efficient tumorregression and metastasis prevention. The battlefield transfer strategy wouldnot only present meaningful insights for immunotherapy, but also realizesubstantial breakthroughs in biomimetic nanotechnology.

【全文链接】https://onlinelibrary.wiley.com/doi/10.1002/smll.202002138