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Enzyme therapeutics have great potential for the treatment of systemic disorders such as urolithiasis and nephrocalcinosis, which are caused by the excessive accumulation of oxalate. However, exogenous enzymes have short half-lives in vivo and elicit high immunogenicity, which largely limit the therapeutic outcomes. Herein, we report a delivery strategy whereby therapeutic enzymes are encapsulated within a thin zwitterionic polymer shell to form enzyme nanocapsules. The strategy is exemplified by the encapsulation of oxalate oxidase (OxO) for the treatment of hyperoxaluria, because as-synthesized OxO nanocapsules have a prolonged blood circulation half-life and elicit reduced immunogenicity. Our design of enzyme nanocapsules that enable the systemic delivery of therapeutic enzymes can be extended to various biomedical applications.
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