Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well‐known catalyst in the petrochemistry industry and one of the first antioxidant nanoparticles proposed for medicine. Like other nanoparticles, it is now described as a promising therapeutic alternative, now as threatening to health. Sources of these discrepancies and how this analysis helps to overcome contradictions found for other nanoparticles are summarized and discussed. For the context of this analysis, what has been reported in the liver is reviewed, where many diseases are related to oxidative stress. Since well‐dispersed nanoparticles passively accumulate in liver, it represents a major testing field for the study of new nanomedicines and their clinical translation. Even more, many contradictory works have reported in liver either cerium‐oxide‐associated toxicity or protection against oxidative stress and inflammation. Based on this, finally, the intention is to propose solutions to design improved nanoparticles that will work more precisely in medicine and safely in society. The burgeoning potential of antioxidant nanoparticles in theranostic applications faces apparently contradictory reports of either medical benefits or toxicity. This delays translation to clinical practice. Sources of those discrepancies are summarized focusing on the paradigmatic case of cerium oxide in liver disease. This analysis contributes to overcoming similar discrepancies of other nanoparticles and will enable the design of improved nanomedicines.