The morphologies of ceria nanocrystals play an essential role in determining their redox and catalytic performances in many applications, yet the effects of synthesis variables on the formation of ceria nanoparticles of different morphologies and their related growth mechanisms have not been systematised. The design of these morphologies is underpinned by a range of fundamental parameters, including crystallography, optical mineralogy, the stabilities of exposed crystallographic planes, CeO_2−x stoichiometry, phase equilibria, thermodynamics, defect equilibria, and the crystal growth mechanisms. These features are formalised and the key analytical methods used for analysing defects, particularly the critical oxygen vacancies, are surveyed, with the aim of providing a source of design parameters for the synthesis of nanocrystals, specifically CeO_2−x. However, the most important aspect in the design of CeO_2−x nanocrystals is an understanding of the roles of the main variables used for synthesis. While there is a substantial body of data on CeO_2−x morphologies fabricated using low cerium concentrations ([Ce]) under different experimental conditions, the present work fully maps the effects of the relevant variables on the resultant CeO_2−x morphologies in terms of the commonly used raw materials [Ce] (and [NO₃ ⁻] in Ce(NO₃)₃·6H₂O) as feedstock, [NaOH] as precipitating agent, temperature, and time (as well as the complementary vapour pressure). Through the combination of consideration of the published literature and the generation of key experimental data to fill in the gaps, a complete mechanistic description of the development of the main CeO_2−x morphologies is illustrated. Further, the mechanisms of the conversion of nanochains into the two variants of nanorods, square and hexagonal, have been elucidated through crystallographic reasoning. Other key conclusions for the crystal growth process are the critical roles of (1) the formation of Ce(OH)₄ crystallite nanochains as the precursors of nanorods and (2) the disassembly of the nanorods into Ce(OH)₄ crystallites and NO₃ ⁻-assisted reassembly into nanocubes (and nanospheres) as an unrecognised intermediate stage of crystal growth.

Cerium-based nanoparticles (CeNPs), particularly cerium oxide (CeO₂), have been studied extensively for their antioxidant and prooxidant properties. However, their complete redox and enzyme-mimetic mechanisms of therapeutic action at the molecular level remain elusive, constraining their potential for clinical translation. Although the therapeutic effects of both antioxidant and prooxidant mechanisms generally are attributed to Ce³⁺ ↔ Ce⁴⁺ redox switching mediation, some studies have hinted at the involvement of unknown pathways in therapeutic effects. While redox switching is recognised increasingly as playing a key role in ROS-dependent cancer therapy, ROS-independent cytotoxicity mechanisms, such as Ce⁴⁺ dissolution and autophagy, also are emerging as being of importance. Although ROS-mediated prooxidant therapies are the most intensively studied, particularly in the context of cancer, the antioxidant activity deriving from the redox switching, particularly during radiation therapy, also plays an important role in the protection of normal cells during radiation therapy, hence reducing adverse effects. Since cancer cell proliferation results in aberrant behaviour of the tumour microenvironment (TME), then CeNP-based therapies are being used to address a multiplicity of known and unknown factors that aim to normalise the TME and thus prevent this aberrant behaviour. Although it is perceived that the pH plays a key role in the therapeutic performance of cerium-based nanoparticles, this is not conclusive because the relative importances of other factors, particularly Ce dissolution, Ce³⁺/Ce⁴⁺ ratio, cellular H₂O₂ level, and the role of anions, remain poorly understood. Consequently, the present work explores these multiple chemistry-driven mechanisms, which are both ROS-dependent and ROS-independent, in cancer therapy.

The present work provides guidelines for the engineering of oxygen vacancy concentrations using morphology-maps based on the characteristics of nanoceria (CeO_2−x) nanocubes, nanorods, and truncated nanooctahedra.