Facilitating Translational Nanomedicine via Predictive Safety Assessment

Abstract

Extensive research on engineered nanomaterials (ENMs) has led to the development of numerous nano-based formulations for theranostic purposes. Although some nano-based drug delivery systems already exist on the market, growing numbers of newly designed ENMs exhibit improved physicochemical properties and are being assessed in preclinical stages. While these ENMs are designed to improve the efficacy of current nano-based therapeutic or imaging systems, it is necessary to thoroughly determine their safety profiles for successful clinical applications. As such, our aim in this mini-review is to discuss the current knowledge on predictive safety and structure-activity relationship (SAR) analysis of major ENMs at the developing stage, as well as the necessity of additional long-term toxicological analysis that would help to facilitate their transition into clinical practices. We focus on how the interaction of these nanomaterials with cells would trigger signaling pathways as molecular initiating events that lead to adverse outcomes. These mechanistic understandings would help to design safer ENMs with improved therapeutic efficacy in clinical settings.

Keywords: adverse outcome pathway (AOP); engineered nanomaterial (ENM); nanomedicine; nanosafety; predictive toxicology; safer design; structure-activity relationship (SAR).

Graphical abstract

Figure 1

Major Exposure Routes of ENMs with Distinct Physicochemical Properties for Medicinal Applications Physicochemical properties of ENMs and their route of administration determine their interaction at the nano-bio interface and cytotoxicity.

Figure 2

SARs Linking ENM Physicochemical Properties to Adverse Outcome Pathways Examples of ENM-induced toxicity mechanisms include lysosomal damage by cationic nanocarriers, NLRP3 inflammasome activation for REO NPs and high aspect ratio nanomaterials, membrane perturbation by 2D nanomaterials and Si-NPs, and lipid peroxidation and ROS generation by silver and metal oxide NPs.