Green Stealth Engineering of Lifetime-Biocatalytic Nanocatalyst for Neuroblastoma Therapy

Although the intrinsic properties of biocatalytic nanomaterials have led to their increasing importance for biomedical applications, their applicability has been hindered by the disadvantages of (1) environmentally deleterious synthesis procedures, (2) non-biocompatibility of conventional surface functionalising agents, (3) lack of stealth properties, and (4) blockage of biocatalytically active surface sites during synthesis, functionalisation, and application. The present work reports a new green stealth engineering strategy, using environmentally-friendly natural materials green synthesis technique, and stimuli-responsive molecules for the development of biocompatible ceria-based nanocatalysts with lifetime biocatalytic properties. This green and stealth technique has the advantages of being an integrated, one-pot, room-temperature synthesis and surface modification method involving surfactant-free precipitation, aqueous silanisation, and metal-free O-PET-ATRP surface functionalisation approach. The surface functionalisation represents a stealth and targeted-design approach that leverages a zwitterionic charge-switchable glycopolymeric stealth coating that serves the four functions of being (1) biologically benign, (2) plasma-protein-repulsive in the physiological environment, (3) charge-switchable between physiological environment and tumour microenvironment, and (4) target-specific in the tumour microenvironment. Critically, lifetime catalytic activity is engineered through the avoidance of adsorption of the functionalising and processing species on lattice sites instead of active sites. These processes were monitored by various analytical techniques in order to elucidate the mechanisms of action of the nanoceria while overcoming environmental, processing, and physiological barriers in nanoceria. The outcomes of this new green and stealth engineering strategy provide lifetime retention of nanoceria's surface-active-sites, thereby optimising the catalytic redox activity in the physiological environment of pH 7.4 (antioxidant) and tumour microenvironment pH of 6.2 (prooxidant) for neuroblastoma and other therapies. Importantly, this novel approach in the design and engineering of new materials with optimal performance has the potential to enable widespread applicability in the biomedical field.