Nanoceria‐Triggered Synergetic Drug Release Based on CeO₂‐Capped Mesoporous Silica Host–Guest Interactions and Switchable Enzymatic Activity and Cellular Effects of CeO₂

Abstract

Herein, a pH stimuli-responsive vehicle for intracellular drug delivery using CeO2 capped mesoporous silica nanoparticles (MSN) is reported. β-Cyclodextrin-modified CeO2 nanoparticles could cap onto ferrocene-functionalized mesoporous silica through host-guest interactions. After internalization into A549 cells by a lysosomal pathway, the ferrocenyl moieties are oxidized to ferrocenium ions by CeO2 lids, which could trigger the uncapping of the CeO2 and cause the drugs release. Because of the pH-dependent toxicity, the CeO2 here behaves as a multi-purpose entity that not only acts as a lid but also exhibits a synergistic antitumor effect on cancer cells. Meanwhile, the cell protective effect of CeO2 nanoparticles alone is demonstrated, which ensures that the dissolved CeO2 nanoparticles can be non-toxic to normal cells.

Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications

“…The synthesized CeONP can be bare or wrapped with a coating of protective substances that can be hydrophilic 20 or hydrophobic. 22 For biological use, biocompatible CeONP has been systematically synthesized in pure water 27 or with the protection of polyethylene glycol, 28 dextran, 29 polyacrylic acid, 10 cyclodextrin, 16 glucose 17 and so on. Synthetic methods are important because they determine the solubility, size, surface condition, charge, structural arrangement and morphology of nanoparticles, thus affecting their properties, including catalytic activities.…”

“…Inspired by the distinctive and multifaceted properties of CeONP, a multifunctional CeONP-capped mesoporous silica nanoparticle (MSN) anticancer drug delivery system was designed by Qu and colleagues 16 ( Figure 8A). They synthesized b-cyclodextrin-modified CeONP and ferrocene-functionalized MSN.…”

“…6 In industry, it has been most widely used as an active component in processes such as three-way catalysts 7 for automobile exhaust-gas treatments, oxidative coupling of methane and water-gas shift reaction. Recently, CeONP has been reported to have multienzyme, including superoxide oxidase, catalase and oxidase, mimetic properties, and has emerged as a fascinating and lucrative material in biological fields such as in bioanalysis, [10][11][12][13][14][15] biomedicine, 9 drug delivery 16,17 and bioscaffolding. 18,19 This review provides a comprehensive introduction to CeONP's catalytic mechanisms, multienzyme-like activities and potential applications in biological fields.…”

Ceria Nanoparticles as Enzyme Mimetics

“…The utilization of nanoceria as oxidase under some special circumstances was also reported. Recently, nanoceria have been used for several applications either in biotic conditions or abiotic conditions, such as antioxidants, [63][64][65] capping [36] and neuroprotection agents, [66][67][68][69][70][71][72] biosensors, [23,28,73] immunoassays, [31,32,74] color indicator [27,[75][76][77][78][79] and so on.…”

“…However, several reports showed that nanoceria would gradually lose their activity due to the changed surface chemistry during the catalysis, [29,30] and the regeneration of catalytic activity may take several days or even weeks. In spite of those, the reactivity of nanoceria toward ROS has offered a variety of applications in biological fields such as bioanalysis, [31][32][33][34] biomedicine, [35] drug delivery, [36,37] and bioscaffolding. [38,39] It has been generally accepted that the enzyme mimetic properties of nanoceria are attributed to the presence of oxygen vacancies and the mixed valence states of Ce 3＋ and Ce 4＋ .…”