Polymer bioconjugates

Considering the rate at which synthetic capabilities have evolved in macromolecular chemistry over the last two decades, it is no surprise that a growing number of researchers have decided to complement or enhance the evolved functionality of biological (macro)molecules by conjugation to well-defined and/or highly functional synthetic polymers. Functionalization with polymers can provide improved stability, solubility, trafficking pathways, and therapeutic potential to already useful biomolecules for a variety of applications.

Polymer–protein and polymer–peptide conjugates have a relatively long history of being used therapeutically, with the polymer actively providing a mechanism to tune the bioactivity of the biomolecule or passively stabilizing the biomolecules in vivo to allow increased blood circulation time or improved tumor targeting by the enhanced permeation and retention effect. Traditionally, the polymer employed has been poly(ethylene glycol) (PEG) or its derivatives because of its nontoxic, nonimmunogenic, and biocompatible properties. However, recently there has been considerable interest dedicated to alternative methods of “PEGylation” by the polymerization of PEG or oligo(ethylene glycol) (OEG) vinyl macromonomers. Many of these methods allow the preparation of polymers that are both biocompatible and stimuli-responsive. Increasingly, polymer bioconjugates with therapeutic potential are being made with other examples of synthetic polymers. Similar to PEG, these polymers may also enhance the stability and solubility of the biological component to which they are attached, while simultaneously providing responsive behavior and numerous sites for subsequent functionalization (e.g., to allow the attachment of cofactors, targeting ligands, imaging reagents, etc.). Due to the ongoing development of bio-orthogonal click chemistry methods, bioconjugation has furthermore become increasingly selective, which has led to hybrid structures with improved functional characteristics.

Recently, considerable attention has been dedicated to conjugation of polymers to nucleic acids. The promise of gene therapy for the treatment of a wide variety of diseases is becoming increasingly obvious, and polymers are anticipated to play a crucial role in enhancing the stability, endocytosis, and endosomal release capability of nucleic acid therapeutics.

While many of the advantages of polymer bioconjugates are most obvious within the areas of drug delivery, imaging, biodiagnostics, etc., these hybrids are also interesting from a materials point of view. The amazing ability of nucleic acids, proteins, peptides, and polysaccharides to assemble into ordered arrays and cause hierarchical complexity in biological systems can be complemented by the structural, economic, and functional advantages associated with synthetic polymers. Indeed, polymer bioconjugates are ideally suited for the preparation of new specialty materials, many of which have well-defined structure on the nanoscale as a result of the programmed assembly behavior of the biological component. While the biomolecule can provide hierarchical organization or favorable interactions for other biological applications, the synthetic polymer component can provide responsive behavior, enhanced structural integrity, and economic feasibility. As a result of the introduction of well-defined polypeptide synthesis methods such as NCA polymerization or protein engineering, the traditional differences between synthetic polymers and biomolecules are beginning to fade. The application of techniques usually associated with the life sciences into polymer chemistry illustrates the highly interdisciplinary character the field of bioconjugation has attained.

The communications, articles, and reviews contained in this themed issue of Polymer Chemistry include many of the most exciting advances in the area of bioconjugation. Some of the contributions describe novel elegant synthetic approaches that can enable the preparation of a variety of new bioconjugates via, for example, site-specific conjugation with well-defined polymers. Other reports focus on new advances or reviews of specific applications including drug/gene delivery, degradable materials, and hybrid structural materials. It is with great pleasure that we have served as guest editors, and we hope this themed issue of Polymer Chemistry will serve as a valuable resource for both newcomers and experts in the field.

Jan van Hest
Brent Sumerlin

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