Zwitterionic Nanocages Overcome the Efficacy Loss of Biologic Drugs

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 30(2018), 14 vom: 15. Apr., Seite e1705728
1. Verfasser: Li, Bowen (VerfasserIn)
Weitere Verfasser: Yuan, Zhefan, Zhang, Peng, Sinclair, Andrew, Jain, Priyesh, Wu, Kan, Tsao, Caroline, Xie, Jingyi, Hung, Hsiang-Chieh, Lin, Xiaojie, Bai, Tao, Jiang, Shaoyi
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article anti-PEG antibody efficacy immunogenicity uricase zwitterionic nanocages Antibodies Biological Products Pharmaceutical Preparations Polymers Proteins
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520 |a For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself. However, it is unclear if the improved immunologic profiles can translate to better clinical outcomes since improved immunogenicity cannot directly reflect amelioration in efficacy. Here, a PCB nanocage (PCB NC) is developed, which can physically encase proteins while keeping their structure intact. PCB NC encapsulation of uricase, a highly immunogenic enzyme, is demonstrated to eradicate all the immune responses. To bridge the gap between immunogenicity and efficacy studies, the therapeutic performance of PCB NC uricase is evaluated and compared with its PEGylated counterpart in a clinical-mimicking gouty rat model to determine any loss of efficacy evoked after five administrations 
650 4 |a Journal Article 
650 4 |a anti-PEG antibody 
650 4 |a efficacy 
650 4 |a immunogenicity 
650 4 |a uricase 
650 4 |a zwitterionic nanocages 
650 7 |a Antibodies  |2 NLM 
650 7 |a Biological Products  |2 NLM 
650 7 |a Pharmaceutical Preparations  |2 NLM 
650 7 |a Polymers  |2 NLM 
650 7 |a Proteins  |2 NLM 
700 1 |a Yuan, Zhefan  |e verfasserin  |4 aut 
700 1 |a Zhang, Peng  |e verfasserin  |4 aut 
700 1 |a Sinclair, Andrew  |e verfasserin  |4 aut 
700 1 |a Jain, Priyesh  |e verfasserin  |4 aut 
700 1 |a Wu, Kan  |e verfasserin  |4 aut 
700 1 |a Tsao, Caroline  |e verfasserin  |4 aut 
700 1 |a Xie, Jingyi  |e verfasserin  |4 aut 
700 1 |a Hung, Hsiang-Chieh  |e verfasserin  |4 aut 
700 1 |a Lin, Xiaojie  |e verfasserin  |4 aut 
700 1 |a Bai, Tao  |e verfasserin  |4 aut 
700 1 |a Jiang, Shaoyi  |e verfasserin  |4 aut 
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773 1 8 |g volume:30  |g year:2018  |g number:14  |g day:15  |g month:04  |g pages:e1705728 
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