A Biomimetic Nanogenerator of Reactive Nitrogen Species Based on Battlefield Transfer Strategy for Enhanced Immunotherapy

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2020-06, Vol.16 (25), p.e2002138-n/a
• Main Authors: Feng, Qianhua, Li, Yuzhen, Wang, Ning, Hao, Yutong, Chang, Junbiao, Wang, Zeying, Zhang, Xueli, Zhang, Zhenzhong, Wang, Lei
• Format: Article
• Language: English
• Subjects: Battlefields; biomimetic; Biomimetics; Cell membranes; Electric power generation; Erythrocytes; Hemoglobin; Hypoxia; Immunotherapy; Nanogenerators; Nanoparticles; Nanotechnology; nitrite reductase activity; reactive nitrogen species; Surface properties; Titanium dioxide
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202002138

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. An inner and outer red blood cell (RBC)‐biomimetic antitumor nanoplatform is developed for reactive nitrogen species generation, which replicates both membrane surface properties and intracellular certain therapeutic mechanism of RRx‐001 in hypoxic RBC. Such an idea would transfer the battlefield of RRx‐001 from hypoxic RBC to hypoxic tumor microenvironment, enhancing its combat capability.