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A Biomimetic Nanogenerator of Reactive Nitrogen Species Based on Battlefield Transfer Strategy for Enhanced Immunotherapy
Author(s) -
Feng Qianhua,
Li Yuzhen,
Wang Ning,
Hao Yutong,
Chang Junbiao,
Wang Zeying,
Zhang Xueli,
Zhang Zhenzhong,
Wang Lei
Publication year - 2020
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202002138
Subject(s) - nanoreactor , battlefield , immunotherapy , nanotechnology , biomimetic materials , microbiology and biotechnology , nanoparticle , chemistry , materials science , immune system , biology , immunology , history , ancient history
Currently, cell membrane is always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular activity seems more meaningful. Inspired by the specific killing mechanism of deoxy‐hemoglobin (Hb) dependent drug (RRx‐001) in hypoxic red blood cells (RBC), this work aims to develop an inner and outer RBC‐biomimetic antitumor nanoplatform that replicates both membrane surface properties and intracellularly certain therapeutic mechanisms of RRx‐001 in hypoxic RBC. Herein, RRx‐001 and Hb are introduced into RBC membrane camouflaged TiO 2 nanoparticles. Upon arrival at hypoxic tumor microenvironment (TME), the biomimetic nanoplatform (R@HTR) is activated and triggers a series of reactions to generate reactive nitrogen species (RNS). More importantly, the potent antitumor immunity and immunomodulatory function of RNS in TME are demonstrated. Such an idea would transfer the battlefield of RRx‐001 from hypoxic RBC to hypoxic TME, enhancing its combat capability. As a proof of concept, this biomimetic nanoreactor of RNS exhibits efficient tumor regression and metastasis prevention. The battlefield transfer strategy would not only present meaningful insights for immunotherapy, but also realize substantial breakthroughs in biomimetic nanotechnology.