Journal
SMALL
Volume 16, Issue 25, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202002138
Keywords
biomimetic; hemoglobin; immunotherapy; nitrite reductase activity; reactive nitrogen species
Categories
Funding
- National Natural Science Foundation of China [81673021, 81901878, U1804183, 81874304]
- China Postdoctoral Science Fundation [2019M662553]
- Key Scientific Research Projects Plan of Henan Higher Education Institutions [20A350011]
- Key Scientific and Technological Project of Henan Province [182102310117]
- Key Scientific Research Project (Education Department of Henan Province) [20HASTIT049]
- Research Fund of Zhengzhou University [32211179]
- Modern Analysis and Computer Center of Zhengzhou University
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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 TiO2 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.
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