Assessing regulated cell death modalities as an efficient tool for in vitro nanotoxicity screening: a review

Abstract

Nanomedicine is a fast-growing field of nanotechnology. One of the major obstacles for a wider use of nanomaterials for medical application is the lack of standardized toxicity screening protocols for assessing the safety of newly synthesized nanomaterials. In this review, we focus on less frequently studied nanomaterials-induced regulated cell death (RCD) modalities, including eryptosis, necroptosis, pyroptosis, and ferroptosis, as a tool for in vitro nanomaterials safety evaluation. We summarize the latest insights into the mechanisms that mediate these RCDs in response to nanomaterials exposure. Comprehensive data from reviewed studies suggest that ROS (reactive oxygen species) overproduction and ROS-mediated pathways play a central role in nanomaterials-induced RCDs activation. On the other hand, studies also suggest that individual properties of nanomaterials, including size, shape, or surface charge, could determine specific toxicity pathways with consequent RCD induction as well. We anticipate that the evaluation of RCDs can become one of the mechanism-based screening methods in nanotoxicology. In addition to the toxicity assessment, evaluation of necroptosis-, pyroptosis-, and ferroptosis-promoting capacity of nanomaterials could simultaneously provide useful information for specific medical applications as could be their anti-tumor potential. Moreover, a detailed understanding of molecular mechanisms driving nanomaterials-mediated induction of immunogenic RCDs will substantially aid novel anti-tumor nanodrugs development.

Keywords:

• Nanotoxicology
• nanoparticles
• reactive oxygen species
• regulated cell death

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by the Ministry of Health of Ukraine as a fragment of the project entitled ‘Research of Effectiveness, Mechanisms of Action and Safety of Rare-Earth Orthovanadate Nanoparticles for Optimization of Radiation Therapy in Oncopathology’ (state registration number 0121U110920), by the Charles University in Prague, Czech Republic (PRIMUS/17/MED/9, UNCE/MED/016, Cooperation), and the Czech National Institute for Cancer Research (reg. No. LX22NPO5102).