Safe-by-Design Flame Spray Pyrolysis of SiO2 Nanostructures for Minimizing Acute Toxicity

Reactive oxygen species (ROS) generation is considered as a critical factor in nanosilica's cell toxicity. Herein, we present a method for controlling the ROS generation by nanosilica toward designing safer-to-use nanosilica materials with minimal acute toxicity. The present work demonstrates a one-step process to synthesize nanosilica materials with minimal ROS production, using the flame spray pyrolysis (FSP) technology, which is currently used for industrial production of SiO2. We show that controlling the temperature regime of nano-SiO2 synthesis in the FSP process allows passivation of the nanosilica surface and, subsequently, control of the ROS production capacity. In this context, using FSP, we have engineered in situ three types of nanosilica materials produced either under high-temperature combustion (ordinarily fumed SiO2) or low-temperature combustion (rSiO2) as well as their combination in a core–shell configuration (rSiO2@SiO2). Electron paramagnetic resonance and Raman spectroscopies were used to study the correlation between ROS formation and the structure of siloxane rings of the silica network. In parallel, the acute toxicity of the particles was monitored by Microtox (Aliivibrio fischeri). Our data show that the acute toxicity and ROS are both correlated with the FSP temperature regime according to the sequence SiO2 ≫ rSiO2@SiO2 > rSiO2. A comprehensive physicochemical mechanism is discussed, which relates the surface-ring structure of nano-SiO2 with ROS yield and acute toxicity. The present findings and the FSP methodology provide a more general easy-to-apply road map for safe-by-design production of metal oxides for issues related to ROS toxicity.