Impact of morphology and collagen-functionalization on the redox equilibria of nanoceria for cancer therapies

Wen-Fan Chen; Chantelle Marie De Sa Malacco; Rashid Mehmood; Kochurani K Johnson; Jia-Lin Yang; Charles Christopher Sorrell; Pramod Koshy

doi:10.1016/j.msec.2020.111663

Impact of morphology and collagen-functionalization on the redox equilibria of nanoceria for cancer therapies

Mater Sci Eng C Mater Biol Appl. 2021 Jan:120:111663. doi: 10.1016/j.msec.2020.111663. Epub 2020 Oct 22.

Authors

Wen-Fan Chen¹, Chantelle Marie De Sa Malacco², Rashid Mehmood³, Kochurani K Johnson², Jia-Lin Yang⁴, Charles Christopher Sorrell², Pramod Koshy⁵

Affiliations

¹ School of Materials Science and Engineering, UNSW Sydney, Sydney, NSW 2052, Australia; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
² School of Materials Science and Engineering, UNSW Sydney, Sydney, NSW 2052, Australia.
³ School of Materials Science and Engineering, UNSW Sydney, Sydney, NSW 2052, Australia; School of Chemical Engineering, UNSW Sydney, Sydney, NSW 2052, Australia.
⁴ Prince of Wales Clinical School, Lowy Cancer Research Centre, School of Medical Sciences, UNSW Sydney, Sydney, NSW 2052, Australia.
⁵ School of Materials Science and Engineering, UNSW Sydney, Sydney, NSW 2052, Australia. Electronic address: koshy@unsw.edu.au.

PMID: 33545829
DOI: 10.1016/j.msec.2020.111663

Abstract

The application of nanoparticulate therapies for cancer depends largely on the uptake and redox activity of the particles. The present work reports the fabrication of different morphologies of nanoceria (CeO_2-x) as nanooctahedra (NO), nanorods (NR), and nanocubes (NC) by hydrothermal synthesis at different temperatures (100 °C, 180 °C) of solutions of 0.05 M Ce(NO₃)₃·6H₂O and different concentrations of NaOH (0.01 M, 6.00 M). The characteristics of these nanomorphologies are compared in terms of the crystallinity (XRD), grain size (TEM), surface area (BET), tendency to agglomerate, and the oxygen vacancy concentration ([V_O^••]) as reflected by the [Ce³⁺]/[Ce⁴⁺] ratio (XPS). The effects of these parameters on the potential cellular uptake are canvassed, suggesting that the nonpolarity of the {111} planes of NO and NR facilitate the preferential uptake of these nanomorphologies. These experimental variables then were normalized through the use of NC as a model substrate for the functionalization using gum arabic (GA) and collagen in order to assess their roles in enhancing redox activity. Both the unfunctionalized and functionalized NC were noncytotoxic in in vitro tests with Kuramochi ovarian cancer cells. However, the antioxidant behavior of the collagen-functionalized NC was superior to that of the unfunctionalized NC, which was superior to that of the controls. These results demonstrate that, while the intrinsic V_O^•• of CeO_2-x enhance the destruction of reactive oxygen species (ROS), functionalization by gum arabic and collagen crosslinking as extrinsic additions to the system enhances ROS destruction to an even greater extent. The antioxidant behavior and potential to neutralize superoxide and hydroxyl radicals of these materials offers new potential for the improvement of nanoparticulate cancer therapies.

Keywords: Ceria; Collagen; Cytotoxicity; Gum arabic; Hydrothermal; ROS production.

MeSH terms

Cerium*
Collagen
Nanoparticles*
Neoplasms* / drug therapy
Oxidation-Reduction

Substances

Cerium
ceric oxide
Collagen