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Confinement of therapeutic enzymes in selectively permeable polymer vesicles by polymerization-induced self-assembly (PISA) reduces antibody binding and proteolytic susceptibility
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Blackman, Lewis D., Varlas, Spyridon, Arno, Maria Chiara, Houston, Zachary H., Fletcher, Nicholas L., Thurecht, Kristofer J., Hasan, Muhammad, Gibson, Matthew I. and O’Reilly, Rachel K. (2018) Confinement of therapeutic enzymes in selectively permeable polymer vesicles by polymerization-induced self-assembly (PISA) reduces antibody binding and proteolytic susceptibility. ACS Central Science, 4 (6). pp. 718-723. doi:10.1021/acscentsci.8b00168 ISSN 2374-7943.
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WRAP-Confinement-of-therapeutic-enzymes-in-selactively-permiable-Blackman-2018.pdf - Published Version - Requires a PDF viewer. Download (3414Kb) | Preview |
Official URL: http://dx.doi.org/10.1021/acscentsci.8b00168
Abstract
Covalent PEGylation of biologics has been widely employed to reduce immunogenicity, while improving stability and half-life in vivo. This approach requires covalent protein modification, creating a new entity. An alternative approach is stabilization by encapsulation into polymersomes; however this typically requires multiple steps, and the segregation requires the vesicles to be permeable to retain function. Herein, we demonstrate the one-pot synthesis of therapeutic enzyme-loaded vesicles with size-selective permeability using polymerization-induced self-assembly (PISA) enabling the encapsulated enzyme to function from within a confined domain. This strategy increased the proteolytic stability and reduced antibody recognition compared to the free protein or a PEGylated conjugate, thereby reducing potential dose frequency and the risk of immune response. Finally, the efficacy of encapsulated l-asparaginase (clinically used for leukemia treatment) against a cancer line was demonstrated, and its biodistribution and circulation behavior in vivo was compared to the free enzyme, highlighting this methodology as an attractive alternative to the covalent PEGylation of enzymes.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||
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Subjects: | Q Science > QD Chemistry R Medicine > RS Pharmacy and materia medica |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||||||||||||||||||||||
SWORD Depositor: | Library Publications Router | ||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Biologicals, Coated vesicles, Immunoglobulins, Enzymes, Polymerization | ||||||||||||||||||||||||||||||
Journal or Publication Title: | ACS Central Science | ||||||||||||||||||||||||||||||
Publisher: | ACS | ||||||||||||||||||||||||||||||
ISSN: | 2374-7943 | ||||||||||||||||||||||||||||||
Official Date: | 27 June 2018 | ||||||||||||||||||||||||||||||
Dates: |
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Volume: | 4 | ||||||||||||||||||||||||||||||
Number: | 6 | ||||||||||||||||||||||||||||||
Page Range: | pp. 718-723 | ||||||||||||||||||||||||||||||
DOI: | 10.1021/acscentsci.8b00168 | ||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||
Reuse Statement (publisher, data, author rights): | Licence for VoR version of this article starting on 16-05-2018: http://pubs.acs.org/page/policy/authorchoice_termsofuse.html | ||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||
Date of first compliant deposit: | 29 May 2018 | ||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 1 June 2018 | ||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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