Review of emerging concepts in nanotoxicology: opportunities and challenges for safer nanomaterial design.

Nanotoxicology and nanosafety has been a topic of intensive research for about more than 20 years. Nearly 10 000 research papers have been published on the topic, yet there exists a gap in terms of understanding and ways to harmonize nanorisk assessment. In this review, we revisit critically ignored parameters of nanoscale materials (e.g. band gap factor, phase instability and silver leaching problem, defect and instability plasmonic versus inorganic particles) versus their biological counterparts (cell batch-to-batch heterogeneity, biological barrier model design, cellular functional characteristics) which yield variability and nonuniformity in results. We also emphasize system biology approaches to integrate the high throughput screening methods coupled with in vivo and in silico modeling to ensure quality in nanosafety research. We emphasize and highlight the recommendation regarding bridging the mechanistic gaps in fundamental research and predictive biological response in nanotoxicology. The research community has to develop visions to predict the unforeseen problems that do not exist yet in context with nanotoxicity and public health hazards due to the burgeoning use of nanomaterial in consumer's product.