We review the apparent discrepancies between studies that report anti-inflammatory effects of cerium oxide nanoparticles (CeO2 NPs) through their reactive oxygen species-chelating properties and immunological studies highlighting their toxicity. We observe that several underappreciated parameters, such as aggregation size and degree of impurity, are critical determinants that need to be carefully addressed to better understand the NP biological effects in order to unleash their potential clinical benefits. This is because NPs can evolve toward different states, depending on the environment where they have been dispersed and how they have been dispersed. As a consequence, final characteristics of NPs can be very different from what was initially designed and produced in the laboratory. Thus, aggregation, corrosion, and interaction with extracellular matrix proteins critically modify NP features and fate. These modifications depend to a large extent on the characteristics of the biological media in which the NPs are dispersed. As a consequence, when reviewing the scientific literature, it seems that the aggregation state of NPs, which depends on the characteristics of the dispersing media, may be more significant than the composition or original size of the NPs. In this work, we focus on CeO2 NPs, which are reported sometimes to be protective and anti-inflammatory, and sometimes toxic and pro-inflammatory.

Chemotherapeutic agents have limited efficacy and resistance to them limits today and will limit tomorrow our capabilities of cure. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumours. In front of this, multimodality has appeared as a promising strategy to overcome resistance. In this context, the use of nanoparticle-based platforms enables many possibilities to address cancer resistance mechanisms. Nanoparticles can act as carriers and substrates for different ligands and biologically active molecules, antennas for imaging, thermal and radiotherapy and, at the same time, they can be effectors by themselves. This enables their use in multimodal therapies to overcome the wall of resistance where conventional medicine crash as ageing of the population advance. In this work, we review the cancer resistance mechanisms and the advantages of inorganic nanomaterials to enable multimodality against them. In addition, we comment on the need of a profound understanding of what happens to the nanoparticle-based platforms in the biological environment for those possibilities to become a reality.

Increased oxidative stress in the retina and retinal pigment epithelium is implicated in age-related macular degeneration (AMD). Antioxidant cerium oxide nanoparticles (CeO2NPs) have been used to treat degenerative retinal pathologies in animal models, although their delivery route is not ideal for chronic patient treatment. In this work, we prepared a formulation for ocular topical delivery that contains small (3 nm), nonaggregated biocompatible CeO2NPs. In vitro results indicate the biocompatible and protective character of the CeO2NPs, reducing oxidative stress in ARPE19 cells and inhibiting neovascularization related to pathological angiogenesis in both HUVEC and in in vitro models of neovascular growth. In the in vivo experiments, we observed the capacity of CeO2NPs to reach the retina after topical delivery and a subsequent reversion of the altered retinal transcriptome of the retinal degenerative mouse model DKOrd8 toward that of healthy control mice, together with signs of decreased inflammation and arrest of degeneration. Furthermore, CeO2NP eye drops’ treatment reduced laser-induced choroidal neovascular lesions in mice by lowering VEGF and increasing PEDF levels. These results indicate that CeO2NP eye drops are a beneficial antioxidant and neuroprotective treatment for both dry and wet forms of AMD disease.

Sodium citrate-stabilized gold nanoparticles (AuNPs) are destabilized when dispersed in cell culture media (CCMs). This may promote their aggregation and subsequent sedimentation, or under the proper conditions, their interaction with dispersed proteins can lead to the formation of a NP-stabilizing protein corona. CCMs are ionic solutions that contain growth substances which are typically supplemented, in addition to serum, with different substances such as dyes, antioxidants, and antibiotics. In this study, the impact of phenol red, penicillin–streptomycin, l-glutamine, and β-mercaptoethanol on the formation of the NP–protein corona in CCMs was investigated. Similar protein coronas were obtained except in the presence of antibiotics. Under these conditions, the protein corona took more time to be formed, and its density and composition were altered, as indicated by UV–vis spectroscopy, Z potential, dynamic light scattering, and liquid chromatography–mass spectrometry analyses. As a consequence of these modifications, a significantly different AuNP cellular uptake was measured, showing that NP uptake increased as did the NP aggregate formation. AuNP uptake studies performed in the presence of clathrin- and caveolin-mediated endocytosis inhibitors showed that neither clathrin receptors nor lipid rafts were significantly involved in the internalization mechanism. These results suggest that in these conditions, NP aggregation is the main mechanism responsible for their cellular uptake.