Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors

• Published in: Nature communications 2018-08, Vol.9 (1), p.3334-14, Article 3334
• Main Authors: Wang, Zhenzhen, Zhang, Yan, Ju, Enguo, Liu, Zhen, Cao, Fangfang, Chen, Zhaowei, Ren, Jinsong, Qu, Xiaogang
• Format: Article
• Language: English
• Subjects: 13/31; 631/67/1059; 639/301/357/354; 692/699/67; 692/700/155; Animals; Apoptosis; Biomimetics; Cascade chemical reactions; Catalase; Catalysis; Cell Death; Cell Line, Tumor; Chemical reactions; External stimuli; Humanities and Social Sciences; Hypoxia; Injections, Intravenous; Intracellular; Manganese Compounds - chemistry; Manganese dioxide; Mice; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Neoplasia; Neoplasms; Oxidation-Reduction; Oxides - chemistry; Reactive oxygen species; Reactive Oxygen Species - metabolism; Science; Science (multidisciplinary); Self-assembly; Spheroids, Cellular - pathology; Stimuli; Tumor Hypoxia; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05798-x

Reactive oxygen species (ROS)-induced apoptosis is a promising treatment strategy for malignant neoplasms. However, current systems are highly dependent on oxygen status and/or external stimuli to generate ROS, which greatly limit their therapeutic efficacy particularly in hypoxic tumors. Herein, we develop a biomimetic nanoflower based on self-assembly of nanozymes that can catalyze a cascade of intracellular biochemical reactions to produce ROS in both normoxic and hypoxic conditions without any external stimuli. In our formulation, PtCo nanoparticles are firstly synthesized and used to direct the growth of MnO 2 . By adjusting the ratio of reactants, highly-ordered MnO 2 @PtCo nanoflowers with excellent catalytic efficiency are obtained, where PtCo behaves as oxidase mimic and MnO 2 functions as catalase mimic. In this way, the well-defined MnO 2 @PtCo nanoflowers not only can relieve hypoxic condition but also induce cell apoptosis significantly through ROS-mediated mechanism, thereby resulting in remarkable and specific inhibition of tumor growth. Hypoxic tumors are resistant to dynamic therapy, limiting potential treatment options. Here, the authors describe a nanoflower where oxidase mimicking PtCo nanoparticles are decorated with catalase mimicking MnO 2 to reverse tumor hypoxia and generate reactive oxygen species for dynamic therapy.