Antioxidant cerium oxide nanoparticle hydrogels for cellular encapsulation

Abstract

Oxidative stress and the resulting radical by-products cause significant toxicity and graft loss in cellular transplantation. Here, the engineering of an auto-catalytic, antioxidant, self-renewing cerium oxide nanoparticle (CONP)-composite hydrogel is reported. This enzyme-mimetic material ubiquitously scavenges ambient free radicals, with the potential to provide indefinite antioxidant protection. Here, we evaluated the potential of this system to enhance the protection of encapsulated beta cells. Co-incubation of CONPs, free in solution with beta cells, demonstrated potent cytoprotection from superoxide exposure; however, phagocytosis of the CONPs by the beta cells resulted in cytotoxicity at concentrations as low as 1 mM. When CONPs were embedded within alginate hydrogels, the composite hydrogel provided cytoprotection to encapsulated beta cells from free radical attack without cytotoxicity, even up to 10 mM concentrations. This nanocomposite hydrogel has wide applicability in cellular transplantation, with the unique advantage of localization of these potent antioxidant CONPs and their capacity for sustained, long-term scavenging.

Toxicity and Protective Effects of Cerium Oxide Nanoparticles (Nanoceria) Depending on Their Preparation Method, Particle Size, Cell Type, and Exposure Route

“…On the other hand, it was observed that when no cytotoxicity is observed, the cellular uptake can even enhance the protection against ROS, and thus reduce apoptosis. [50] These different reports demonstrated various protective as well as toxic effects for nanoceria, as already pointed out in other reviews on other nanomaterials as well. [6,28,32,51] Furthermore, the combination of materials, for example the use of nanoceria with other particles such as those in diesel exhaust, may increase their toxicity [52] and render the biosafety of nanoceria more challenging to determine.…”

“…[48,49] Cytotoxic effects of nanoceria can be greatly reduced by preventing the internalization of the NPs into cells, for example by encapsulating them into a hydrogel. Weaver and Stabler [50] demonstrated that their alginate hydrogel prevented the phagocytosis of dextran-coated nanoceria and thus reduced their cytotoxicity, while preserving the antioxidative and protective properties of these particles. On the other hand, it was observed that when no cytotoxicity is observed, the cellular uptake can even enhance the protection against ROS, and thus reduce apoptosis.…”

Increased viability of fibroblasts when pretreated with ceria nanoparticles during serum deprivation

“…Hence, it is possible to define oxidative stress as the disproportion between the production of these species, such as hydrogen peroxide and superoxide, and their elimination through antioxidant enzymes that are present on human tissues, such as catalase and superoxide dismutase. 5 This imbalance often results in the destruction or dysfunction of cellular structures, causing pathological disorders. The prevention of these pathophysiological conditions is a main goal in the field of nanomedicine.…”

Biomaterial‐Based Metabolic Regulation in Regenerative Engineering

“…Another way for biomaterials to collect cell-generated ROS to maintain redox homeostasis is derived from the capability of the material components to directly react with extracellular ROS [106] or to mediate the conversion of noxious free radicals to a nontoxic counterpart. [107] For example, cerium oxide nanoparticles (CONP) are known for their self-renewing ability of redox cycle between Ce 3+ and Ce 4+ valence states, and for the potential to quench multiple types of free radicals. [108] Addition of CONP at a concentration of 0.1 × 10 −3 m into culture medium already potently protected β cells from oxidative damage.…”

“…While using the composite system for β cell delivery, the presence of CONP in hydrogel provided protection to encapsulated cells without causing cytotoxicity, even when its concentration reached 10 × 10 −3 m, which demonstrated its capability in preventing internalization of CONP by cells and in protecting the encapsulated β cells from free radical attack demonstrating its applicability in cell transplantation. [107]…”