Editorial for Virtual Issue on Polymer Bioconjugates in Biology and Medicine

Medicine T interface between polymer science and bioconjugate chemistry is home to an active group of scientists who seek to combine the best of both worlds: the chemical versatility of polymeric architectures with the biological function of naturally occurring molecules. Of course, the huge success of protein pegylation has already demonstrated the great potential of this interdisciplinary research area, which does not imply that it has reached a state of maturation. On the contrary, in recent years, novel methodologies have been developed both in the area of polymer science and in the field of bioconjugate chemistry, which have now opened up opportunities to construct conjugates with an unprecedented level of control. Traditional approaches, such as pegylation, are revisited and improved; site-selective conjugation of polymers of defined length clearly enhances the reproducibility and activity of the conjugates. A significant body of work is now in place to aid those interested in preparing new polymer−biomolecule conjugates. A diverse toolbox of immobilization, functionalization, and polymerization chemistries has been developed that allows access to well-defined, controlled architecture polymer conjugates with proteins, peptides, antibodies, polysaccharides, and nucleic acids, among others. Advances in aqueous polymerizations and in the development of polymerization or ligation methodologies that require no (or only miniscule amounts of) metal catalysts now enable the synthesis of conjugates that offer potential in the foreseeable future as therapeutics, catalysts, and new biohybrid materials. The selected group of recent publications in the Virtual Issue entitled “Polymer Bioconjugates in Biology and Medicine” offers evidence of this progress and serves as an example of how the advances of the last half-decade in polymer synthesis can be combined with the evolved sophistication of biological macromolecules to access new materials. Moreover, as our ability to access increasingly well-defined bioconjugates grows, we now see major advances in bioconjugate characterization. The latter has proven to be a particularly difficult task over the years. Many of the methods most commonly employed to characterize synthetic polymers are difficult to extend to biological macromolecules that contain a diverse set of functional groups and complex tertiary/ quaternary structure. Similarly, many of the analytical strategies used to characterize biological macromolecules are remarkably precise, yet their extension to polymer bioconjugates is complicated by the relatively broad molecular weight distribution of the synthetic macromolecular component and uncertainty with respect to the immobilization site. It is only relatively recently that we have seen innovative approaches that enhance our ability to observe, understand, and manipulate the self-assembly of polymer bioconjugates in solution and in the bulk. Despite the advances in preparing, understanding, and applying polymer bioconjugates, considerable challenges remain. There is still a great need for innovative solutions to many challenges in the biomedical field. The construction of drug carrier systems with high loading potential and targeting functionality requires macromolecules with multiple separately addressable anchoring groups. In gene therapy, with siRNA delivery and more recently CRISPR/Cas9 technology, the search for the most effective polymer-based delivery vehicle is in full swing. Next to that, scientists attempt to introduce new properties via conjugation, such as enzymes with switchable activity due to the presence of a stimulus-responsive polymer. This diversity is clearly illustrated by the selection of papers that have appeared in the macromolecules family of journals ACS Macro Letters, Biomacromolecules, Macromoleculesand Bioconjugate Chemistry, as well as a couple of compelling review articles from Chemical Reviews. We hope this collection of publications will provide insight into recent developments in the area while also providing inspiration to those seeking to develop the next generation of polymeric bioconjugates. Jan van Hest, Associate Editor Bioconjugate Chemistry Brent Sumerlin, Associate Editor ACS Macro Letters and on behalf of Macromolecules Kristi S. Anseth, Associate Editor Biomacromolecules Molly Shoichet, Associate Editor Biomacromolecules Sharon Hammes-Schiffer, Editor-in-Chief Chemical Reviews