Zwitterionic Nanocages Overcome the Efficacy Loss of Biologic Drugs

• DOI: 10.1002/adma.201705728
• Publication Date: 2018-02-21T16:45:27Z
• Authors: Bowen Li; Zhefan Yuan; Peng Zhang; Andrew Sinclair; Priyesh Jain; Kan Wu; Caroline Tsao; Jingyi Xie; Hsiang‐Chieh Hung; Xiaojie Lin; Tao Bai; Shaoyi Jiang
• Keywords: Nanocages; PEGylation; Clinical efficacy

Abstract For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for failure their treatment. Covalent binding hydrophilic polymers proteins commonly employed mitigate potential responses. However, while this technique proved partially reduce antibodies (Abs) reactive proteins, it may induce Abs toward associated and thus result in loss efficacy. Zwitterionic poly(carboxybetaine) (PCB) recently shown improve immunologic properties without inducing any antipolymer against itself. unclear if improved profiles can translate better clinical outcomes since immunogenicity cannot directly reflect amelioration Here, a PCB nanocage (PCB NC) developed, which physically encase keeping structure intact. NC encapsulation uricase, highly immunogenic enzyme, demonstrated eradicate all To bridge gap between efficacy studies, therapeutic performance uricase evaluated compared with its PEGylated counterpart clinical‐mimicking gouty rat model determine evoked after five administrations.