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Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo
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Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo
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Journal Article
Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo
2014
Overview
In comparison to neutral linear polymers, functional and architecturally complex (that is, non-linear) polymers offer distinct opportunities for enhancing the properties and performance of therapeutic proteins. However, understanding how to harness these parameters is challenging, and studies that capitalize on them
in vivo
are scarce. Here we present an
in vivo
demonstration that modification of a protein with a polymer of appropriate architecture can impart low immunogenicity, with a commensurably low loss of therapeutic activity. These combined properties are inaccessible by conventional strategies using linear polymers. For the model protein
L
-asparaginase, a comb-polymer bio-conjugate significantly outperformed the linear polymer control in terms of lower immune response and more sustained bioactivity. The semi-permeability characteristics of the coatings are consistent with the phase diagram of the polymer, which will facilitate the application of this strategy to other proteins and with other therapeutic models.
The attachment of polymers to protein molecules is known to shield them from biological breakdown. Here, the authors apply this concept to an asparaginase, in order to prevent its deactiviation by host immune responses during leukaemia treatment.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 140/131
/ 631/92
/ 64/60
/ Animals
/ Antineoplastic Agents - administration & dosage
/ Antineoplastic Agents - metabolism
/ Asparaginase - administration & dosage
/ Drug Carriers - pharmacology
/ Enzymes
/ Humanities and Social Sciences
/ Methacrylates - pharmacology
/ Mice
/ Polyethylene Glycols - chemistry
/ Polyethylene Glycols - metabolism
/ Polyethylene Glycols - pharmacology
/ Polymers
/ Proteins
/ Science
