Layer‐by‐Layer Cerium Oxide Nanoparticle Coating for Antioxidant Protection of Encapsulated Beta Cells

Abstract

In type 1 diabetes, the replacement of the destroyed beta cells could restore physiological glucose regulation and eliminate the need for exogenous insulin. Immunoisolation of these foreign cellular transplants via biomaterial encapsulation is widely used to prevent graft rejection. While highly effective in blocking direct cell‐to‐cell contact, nonspecific inflammatory reactions to the implant lead to the overproduction of reactive oxygen species, which contribute to foreign body reaction and encapsulated cell loss. For antioxidant protection, cerium oxide nanoparticles (CONPs) are a self‐renewable, ubiquitous, free radical scavenger currently explored in several biomedical applications. Herein, 2–12 alternating layers of CONP/alginate are assembled onto alginate microbeads containing beta cells using a layer‐by‐layer (LbL) technique. The resulting nanocomposite coatings demonstrate robust antioxidant activity. The degree of cytoprotection correlates with layer number, indicating tunable antioxidant protection. Coating of alginate beads with 12 layers of CONP/alginate provides complete protection to the entrapped beta cells from exposure to 100 × 10−6 m H2O2, with no significant changes in cellular metabolic activity, oxidant capacity, or insulin secretion dynamics, when compared to untreated controls. The flexibility of this LbL method, as well as its nanoscale profile, provides a versatile approach for imparting antioxidant protection to numerous biomedical implants, including beta cell transplantation.

CeO2 Nanoparticle-Containing Polymers for Biomedical Applications: A Review

“…For the antioxidant protection of cells, Abuid et al synthesized alginate microbeads containing β-cells, where two to 12 alternating layers of CeNPs/alginate were assembled onto alginate microbeads using a LbL technique [ 80 ]. These CeNPs/alginate coatings protected cells from ROS-mediated cellular dysfunction, with 12 layers of coatings providing complete preservation of cells’ metabolic activity, glucose stimulated response and antioxidant activity after ROS exposure.…”

Functional recovery of natural killer cell activity by nanoparticle‐mediated delivery of transforming growth factor beta 2 small interfering RNA

“…Also, consideration had to be given to the eventual in vivo applications and requirement of the administered cells to function in the oxidatively stressed tumor microenvironment, which could further inhibit their activity (Conti et al, 2010;Maj et al, 2017). A promising approach to enhancing cell survival under conditions of oxidative stress is through nanomaterials that scavenge reactive oxygen species, such as manganese oxide and cerium oxide (Abuid et al, 2019;Tootoonchi et al, 2017). Manganese dioxide NPs (MnO 2 -NP), which scavenge hydrogen peroxide to produce oxygen, have also been utilized to decrease tumor hypoxia (Song et al, 2016).…”

Nanotechnology Approaches to Modulate Immune Responses to Cell-based Therapies for Type 1 Diabetes

“…127,128 As an alternative, CONP can be integrated within encapsulating biomaterials to serve as a local antioxidant. 127,129 In one approach, CONP was coated with dextran and immobilized within alginate microbeads, where the embedded CONP protected beta-cells from ambient ROS. 127 In another approach, nanoscale coatings of CONP and alginate were generated in a LbL manner.…”

“…127 In another approach, nanoscale coatings of CONP and alginate were generated in a LbL manner. 129 The resulting ultrathin coatings scavenged externally generated ROS, providing protection from ROS-mediated insults to the underlying cells. 129 Overall, the high potential of this material to impart durable and ubiquitous antioxidant protection in cell culture studies supports the translation of these materials to preclinical models.…”