Delivery of amino acid oxidase via catalytic nanocapsules to enable effective tumor inhibition

Abstract

Amino acids are the fundamental building blocks of proteins in tumor cells. The consumption of amino acid can be an effective approach for destroying the tumor cytoskeleton and malfunctioning of the intracellular metabolic balance. Following this concept, herein, amino acid oxidase (AAO) is delivered by hollow Fe³⁺/tannic acid nanocapsules (HFe–TA) and incorporated within the cancer cell membrane (M) for the first time for synergistic tumor therapy. In this system (M@AAO@HFe–TA), the intracellularly delivered AAO molecules catalyze the oxidative deamination effectively and consume amino acids significantly. The upregulation of intracellular acid and H₂O₂ concentration facilitates the HFe–TA mediated Fenton reaction and enhances the induction of cytotoxic ˙OH. With the combined effects, considerable in vitro and in vivo tumor inhibition was achieved by M@AAO@Fe–TA due to the activated Bcl-2/Bax/Cyt C/caspase 3 mitochondrial apoptotic pathway. This study offers an alternative therapeutic platform, functioning as a biomimetic cascade nanozyme, to enable synergistic starvation and chemodynamic tumor therapy with high efficacy.