Biomolecular Densely Grafted Brush Polymers: Oligonucleotides, Oligosaccharides and Oligopeptides

Abstract

In this Minireview, we describe synthetic polymers densely functionalized with sequence-defined biomolecular sidechains. We focus on synthetic brush polymers of oligonucleotides, oligosaccharides, and oligopeptides, prepared via graft-through polymerization from biomolecule functionalized monomers. The resulting structures are brush polymers wherein a biomolecular graft is positioned at each monomer backbone unit. We describe key synthetic milestones, identify synthetic opportunities, and highlight recent advances in the field, including biological applications.

Graphical Abstract

1. Introduction

Nucleic acids and proteins exist in nature as primary, linear sequences of nucleotides and amino acids that then assemble and fold into higher order structures. While DNA and RNA are generally linear in terms of covalent linkages along their backbones, branched multimeric polypeptide structures are highly prevalent in nature, being formed through disulfide crosslinks between primary sequences. In addition, sugars can be found arranged either as linear or branched primary sequences.

Although uncommon in nature, brush polymer type structures have also been described. One such example is aggrecan, (Figure 1),^[1] which is a bottlebrush structure present in the extracellular matrix of cartilage. Proteoglycans are a family of proteins significantly modified with negatively charged glycosaminoglycan (GAG) side chains, which make up to 90% of the polymer mass.^[2] Post-translational conjugation to the protein core occurs at a serine residues, to which GAG is attached through a tetrasaccharide bridge^[3]—an approach a polymer chemist may describe as “graft-to”, wherein an already prepared polymer backbone is reacted with new side-chains. Proteoglycans are important for sustaining tissue structure and hydration by creating a large osmotic pressure via the charged GAGs, drawing water into the tissue.^[3] These structures play important roles in connective tissue, cartilage or extracellular matrix, providing flexibility and elasticity.

Figure 1.

Amplitude AFM images of aggrecan monolayers. (A) Fetal epiphyseal aggrecan. (B) Mature nasal aggrecan. The glycosaminoglycan side chains take on an extended (*) form, or occasionally a collapsed (**) form. Figure adapted from Ref. [1]. Copyright 2003 Elsevier.

Neurofilament (NF) proteins are another biomolecule with a brush architecture.^[4] These filaments run parallel to axons and are fundamental for their radial growth. NFs are composed of three polypeptide subunits named by their respective molecular weight: light (NF-L), medium (NF-M), and heavy (NF-H). The N-terminus of each subunit contains an approximately 300 amino acid long rod domain which associates with the rod domains of the other subunits to form the filament backbone. The C-terminus of NF-M and NF-H each contains a long tail which projects from the backbone to form the NF sidearms. Therefore, the assembled NF has a “bottlebrush” structure in which the core is formed by the filament backbone and the shell is formed by the radially extended densely packed sidearms.^[5]

For proteins, nucleic acids, and polysaccharides, the biopolymers have encoded, informational, primary sequences. This type of sequence control, of course, continues to elude polymer chemists. However, synthetic approaches have allowed the incorporation of sequence defined biomolecules into new architectures to realize a variety of properties distinguishing these bioconjugates from the individual synthetic and biopolymers alone. Key examples come from the literature and clinical utility surrounding protein^[6] and peptide polymer bioconjugates,^[7] of which the most well-known are pegylated protein therapeutics.^[8] Additionally, polymer conjugates of nucleic acids have become interesting in drug delivery applications and in sequence recognition wherein single polymer chains are conjugated at the 3′- or 5′-ends of oligonucleotides.^[9]

In addition to end-on modified peptides and oligonucleotides, the introduction of biomolecules as brushes on synthetic scaffolds has received ongoing interest and attention.^[10] In this Minireview, we focus on this class of densely grafted brush polymers, wherein each graft is a sequence defined biomolecule incorporated as a monomer through graft-through polymerization (Figure 2). These polymers exhibit emergent properties including multivalency, cell penetration, and biomolecule stability, with significant advantages over the individual, unmodified biomolecular oligomers that make up their side chains.

Figure 2.

(A) Synthetic biomolecular brush polymers prepared via graft-through polymerization of biomolecule-functionalized monomers. Sequence defined biomolecular grafts are positioned at each monomer unit. Three examples of biomolecule monomer are shown; (B) oligonucleotide, (C) oligosaccharide, and (D) oligopeptide.

2. Oligonucleotide Brush Polymers

Biomedical applications of synthetic oligonucleotides have attracted significant interest due to their unique properties, including sequence-specific recognition and biological activity.^[11] While highly promising therapeutically, negatively charged oligonucleotides suffer from serious limitations such as poor cellular penetration, reduced bioavailability, and susceptibility to hydrolysis in the presence of nucleases. These inherent downsides of oligonucleotides greatly compromise their effectiveness both in vitro and in vivo and have hindered translation to the clinic. Several approaches towards engineering the structure of oligonucleotides have been developed, giving rise to spherical nucleic acids,^[12] cyclic oligonucleotides,^[13] and polymer-oligonucleotide bioconjugates.^[9b,14] Among these structural variations, oligonucleotide brush polymers hold potential due to their densely packed three-dimensional architecture and ability to display oligonucleotide side chains in a multivalent fashion.^[9a,15]

Both graft-to and graft-through polymerization approaches have been adopted to prepare oligonucleotide brush polymers.^[9a,15a,16] Historically, the graft-to approach involving conjugation of oligonucleotides to a prepared polymer backbone has been more widely utilized.^[14,16a,b] However, conjugation efficiency and final grafting density tend to be limited because of steric bulk and strong charge repulsion among the oligonucleotide side chains. With the advent of functional group-tolerant living polymerization techniques, especially ring-opening metathesis polymerization (ROMP), the graft-through approach has been fruitful.^[17] ROMP of nucleic acid modified monomers has been reported independently by the Gianneschi,^[15b] Herrmann,^[9a] and Zhang groups,^[15a] paving a path for synthesizing well-defined, highly dense oligonucleotide brush polymers (Figure 3).

Figure 3.

Examples of oligonucleotide brush polymers. Each accessible via functional group tolerant ROMP.

The efficacy of oligonucleotide-based biomedicine is highly dependent on the ability to penetrate the cell wall and reach intracellular targets. While free oligonucleotides have rather low rates of cellular uptake, arranging them into a dense and multivalent structure can result in significantly improved cellular uptake and penetration properties.^[15a,18] Recently, Zhang and co-workers harnessed organic phase ROMP to prepare oligonucleotide brush oligomers and polymers with tunable degrees of polymerization (DP) and grafting density (Figure 4).^[15a] Notably, a graft density related cell uptake relationship was established. This was done by evaluating the cellular uptake efficiency of fluorescein-labeled DNA brush polymers with different grafting densities at various DNA concentrations. Confocal microscopy demonstrated that increasing DP and grafting density led to enhanced cell-associated fluorescence. Cellular uptake increased linearly as a function of DNA concentration, with sub-maximum saturation even at high oligonucleotide concentrations of 800 nm, as assessed by flow cytometry. These results confirm a remarkably higher cellular uptake of DNA brush polymer compared to free DNA. While non-functional DNA was used as a proof-of-concept in these studies, it can easily be envisioned how oligonucleotide brush polymers can be synthesized with functional base sequences including antisense oligonucleotides, aptamers, and short interfering RNAs (siRNAs), highlighting their potential as translational biomedical therapeutics.

Figure 4.

(A) Schematic representation of a protected DNA (protDNA) brush polymer. (B) Mean fluorescence of SKOV-3 cancer cells treated with different DNA graft polymers. (C) Uptake rates of DNA brush polymers as a function of DNA surface density. (D) Cellular uptakes of DNA brush polymers with different degree of polymerization (DP). Cell nuclei are stained in blue with DAPI and the polymer is labeled with fluorescein. Figure adapted from Ref. [15a]. Copyright 2019 Elsevier.

In addition to polymerizing therapeutically active oligonucleotides, the complementary base pairing nature of nucleotides allows for the unique capability of being utilized as linkages to conjugate different payloads, such as fluorescent dyes^[19] or antibodies. Matyjaszewski and Das developed a brightly fluorescent nanotag based on a bottle brush polymer which contains hundreds of duplex DNA strands as side chains.^[19] These brush-localized DNA strands serve as a dense scaffold for accommodating thousands of DNA intercalating fluorescent dyes (i.e., YOYO-1). Through DNA hybridization, a secondary antibody was conjugated to the dye-loaded DNA brush polymer, generating an immuno-fluorescent probe that is at least 10 times brighter than commercially available antibodies labeled with Alexa Fluor dyes or quantum dots. Although these structures were accessed via graft-to synthesis, implementation of graft-through methodologies could be adopted to prepare analogous and tunable structures in the future.

Another method to generate oligonucleotide-based brush polymers involves their incorporation into a polymer backbone with other macromolecules arrayed as side chains. One notable example of this technique comes from Mirkin and co-workers, where sequence specific DNA interactions were used to polymerize green fluorescent protein (GFP).^[20] Depending on the sequence and conformation of the attached DNA, GFP-DNA monomers could polymerize through either a step-growth pathway (with single stranded DNA) or a chain-growth pathway (with hairpin DNA). Importantly, the chain-growth/hairpin DNA system demonstrates living polymerization characteristics with addition of fresh monomers able to extend the polymer chain. We note that, rather than being a nucleic acid brush polymer in the sense of the Zhang work described above,^[15a] this approach yields an unusual structure consisting of a nucleic acid primary sequence with a brush of protein. In an analogous example, oligonucleotides were prepared via a graft-to approach, with long PEG side chains resulting in reduced recognition by the innate immune system.^[21] This phenomenon was directly correlated with increased steric congestion, which increased brush polymer assisted compaction and sterically blocked DNA-recognizing, immune activation Toll Like Receptors (TLRs) from binding to the DNA component. These results suggest that the unique globular architecture of the PEGylated DNA brush polymer allows for minimized immune activation, which is advantageous for the design of non-immunogenic oligonucleotide based therapeutics.

The potential of dense DNA brush polymers for biotherapeutic applications has yet to be fully realized. Indeed, very few examples of this kind of architecture exist.^[9b] Given the success of strategies for arraying oligonucleotides on surfaces and on nanoparticle templates,^[18,22] living polymerization approaches for the facile introduction of oligonucleotides at each position on a polymer backbone, should be further investigated. Future applications of this scaffold technology can be envisioned for a wide range of scenarios, including the transportation and delivery of functional DNA, siRNA, and other nucleic acid analogues.

3. Oligosaccharide Brush Polymers

Unlike nucleic acids, which are always arranged as a linear chain of phosphate-linked monomers in nature, sugars can be found natively arrayed as dense brushes. Saccharide-functionalized molecules are naturally abundant for recognition, signaling, and regulatory functions. There has been consistent interest in realizing the inherent value in synthetically replicating this kind of arrangement.^[23]

Since the first demonstrations involving the functional group-tolerant living polymerization of monosaccharide-functionalized monomers,^[24] there has been steadily increasing interest in the preparation of well-defined synthetic glycopolymers through graft-through controlled polymerization (Figure 5). These efforts have focused on the high density display of mono-, di-, and trisaccharide side-chains on synthetic polymer backbones. Initial examples of sugar-functionalized polymers come from Schrock’s pioneering efforts in olefin metathesis, via ROMP (Figure 5A).^[25] In this work, a protected galactose-modified norbornene monomer was polymerized with low dispersity (Ð: 1.06–1.32). Protecting group-free synthetic glycopolymers were prepared by Kiessling and co-workers via ROMP using a Grubbs Generation 1 initiator with high functional group tolerance (Figure 5B).^[24] In turn, Fukuda and co-workers first reported protected glucose-functionalized polymers employing Atom-Transfer Radical Polymerization (ATRP) (Figure 5C).^[26] The first aqueous Reversible Addition Fragmentation Transfer (RAFT) polymerization was demonstrated by McCormick and co-workers in 2003, polymerizing, in a protecting group free approach, a glucose methacrylate monomer (Figure 5D).^[27]

Figure 5.

Mono- and Trisaccharide and β-cyclodextrin functionalized polymers prepared from appropriately modified monomers via ROMP, ATRP and RAFT.

ROMP has proven a versatile method for accessing this class of material, with Buchmeiser and co-workers reporting β-cyclodextrin oligomers (m = 3) (Figure 5E).^[28] In this work, β-cyclodextrin was polymerized and used for chiral separations of enantiomers in capillary electrophoresis. The β-cyclodextrin oligomer exhibited superior enantiomeric resolution capability over the monomer.

Olsen and co-workers reported a mucin-like synthetic glycopolymer in 2016 (Figure 5F).^[29] This material showed improved antiviral activity compared to mucin itself and non-polymeric analogues. This was achieved by the graft-through polymerization of sialic acid (SA)-PEG and oligoethylene glycol-linked norbornene macromonomers and monomers, respectively in a rare example of more complex sugar-type brush polymers accessed via living, graft-through polymerization reactions. The multivalent effect of the densely functionalized SA brush was strongly implicated in the performance of these materials.

Despite considerable progress in graft-through polymerization strategies, the majority of functional materials examined in this space remain based on graft-to polymers functionalized with oligosaccharides. Therefore, classical conjugation chemistry, such as so-called click chemistry, has dominated this work.^[30] The most exciting contributions have involved efforts to mimic the properties of the native glycocalyx,^[31] the native mediator of cell-cell and cell-surface interactions.^[32] Whilst individual protein-saccharide interactions are relatively weak, these may be enhanced by harnessing the cluster glycoside effect, wherein multivalent effects occur.^[33] Thus, by compacting many saccharides onto a single polymer backbone, the strength of specific interactions can be tuned. Control over grafting density and the length of saccharide side chains, can then be used to set the size of the glycoside cluster.^[34] This effect also decreases the number of saccharide units per branch that are needed to produce the desired result.^[35] Thus, the bottlebrush structure has been an ideal target for optimal control over density and arrangement. One such example comes from Bertozzi and co-workers, who have developed a synthetic method via reversible ligation of reducing sugars to a poly(acryloyl hydrazide) backbone, which has been demonstrated for conjugation of trisaccharide functionalities.^[23a] This chemistry has been harnessed for high throughput screening of specific lectin binding.

Synthetic proteoglycans have been engineered to mimic the native cell signaling moieties of the glycocalyx so as to direct cellular growth, repair, and differentiation processes (Figure 6).^[23b] In this work from Godula and co-workers, these synthetic proteoglycans were prepared through a strain-promoted azide-alkyne cycloaddition of the oligosaccharide moiety to a polyacrylamide backbone. The resulting synthetic proteoglycans were introduced to embryonic stem cells, mimicking the native heparan sulfate proteoglycans (HSPGs), where they rescued FGF2-mediated kinase activity, and promoted neural specification. Further, this is a simplified way to synthetically reproduce the properties and effects of more complex native glycopolymers, such as glycosaminoglycans.^[36]

Figure 6.

Synthesis of Neoproteoglycans (neoPGs), which were screened for FGF2 affinity and inserted into plasma membranes of embryonic stem cells, where they effectively replaced the function of native heparan sulfate proteoglycans to promote neural differentiation and remodeling. (A) NeoPGs funtionalized with a phospholipid tail for membrane insertion and an Alexa Fluor 488 (AF488) tag for imaging. (B) NeoPGs 11A, D, and N inserted into membranes of Ext 1−/− mESCs (green) and promoted FGF2 binding according to the structure of their glycans (red). (C) Enhanced FGF2 binding to Ext1−/− mESCs remodeled with neoPG 11D carrying the sulfated diGAG, D2A6, while 11A and 11 N, which have undetectable affinity for FGF2, failed to recruit the growth factor to the cell surface. Figure adapted from Ref. [24b]. Copyright 2014 American Chemical Society.

This emerging class of material is no doubt exciting and will further benefit from the kind of controlled, functional group tolerant polymerization strategies available for incorporating complex biopolymers via graft-through polymerization. Such approaches would allow access to polymers with oligosaccharide side-chains where robust polymerization reactions are relied on, without the need for lower yielding conjugation reactions between multiple high molecular weight building blocks. That is, prepare the most complex monomer first and converge on the polymer directly, capitalizing on rapid and reliable controlled polymerization reactions. The resulting multivalent architectures should give rise to rich properties with relevance in recognition and possibly as structural elements in synthetic materials. Potential applications could include biosensing and chromatography, as they may be versatile and stable platforms for the high-density display of biomolecular ligands.^[37]

4. Oligopeptide Brush Polymers

Since the discovery of solid phase peptide synthesis, these oligomeric biomolecules have found applications in a variety of fields including bio-sensor design,^[38] catalysis,^[39] biology and medicine.^[40] In particular, outstanding properties such as biocompatibility, high selectivity and targeting make peptides excellent candidates as therapeutics.^[41] Despite this promise, chemical and physical instability, poor cellular uptake and low bioavailability, limit their clinical translation.^[42] At the most basic level, the poor activity of many peptide drug candidates results from both rapid renal filtration and fast proteolytic degradation upon administration. These effects translate into short in vivo half-lives and limited effect. Although frequent administration and higher dosages offer the opportunity to restore therapeutic activity, these routes result in more invasive and persistent treatments, raising costs from both the manufacturing standpoint and because of the need for extensive in clinic patient care.

Several approaches have been developed to overcome these weaknesses.^[42,43] Among them, incorporation of unnatural amino acids,^[44] peptide lipidation,^[41d,45] peptide cyclization,^[44b,46] the formation of lactam bridges^[47] and stapling^[41e,48] are well known. In addition, peptide-polymer and more frequently protein-polymer conjugates have become a major class of materials.^[42b,49] Most famously, these have been developed for the clinic in the form of PEGylated proteins,^[8a] with continued advancement in the age of functional group, and mild living polymerization chemistry.^[8c] In each case, the materials are arranged as end-on polymer protein conjugates, with one or more polymer chains linked to a single protein.

Within the general field of peptide-polymer bioconjugates, brush peptide-polymers have attracted attention, with recent contributions employing dual polymerization strategies (Figure 7).^[50] In this work, Wooley and co-workers reported a synthetic polymer brush architecture via graft-through polymerization of polypeptide monomers (Figure 7A). Cheng and co-workers prepared polypeptides via NCA ROP in a graft-from approach from a backbone accessed via ROMP (Figure 7B). In this manner, brush polymers of polypeptides are accessed but without control over the amino acid sequence in the side chain.

Figure 7.

(A) Graft-through polymerization reactions utilizing polypeptide monomers prepared via N-carboxyanhydride (NCA) ROP. (B) A graft-from strategy towards polypeptide brushes. (C) An AFM micrograph of the polymers shown in (B), reveal rigid rod-like structures morphologically reminiscent of proteoglycan structures (e.g. aggregan), on freshly cleaved mica. (D) Length distribution of the polymers from AFM analysis shown in (C). Copyright 2017 American Chemical Society and 2017 Springer Nature Limited.

While the versatility of post-polymerization modification methods have enabled the design of sequence defined peptide-brush polymers for several biological applications,^[51] functional group-tolerant polymerization techniques have been exploited to directly polymerize peptide monomers bypassing synthetic and purification steps and yielding the most efficient, defect free and densely arrayed brushes possible (Figure 8). Grubbs and co-workers first used ROMP to prepare biologically-relevant peptide brush polymers via the graft-through polymerization of a protected pentapeptide (Figure 8A).^[52] Peptide brush polymers bearing the cell surface binding peptide, RGD were successfully polymerized. The resulting polymer brush resulted in enhanced cell adhesion.

Figure 8.

Examples of peptide brush polymers accessed via different graft-through polymerization strategies.

ATRP was also explored for the direct polymerization of elastin mimic peptide sequence (VPGVG, Figure 8B).^[53] This peptide was successfully polymerized into a brush polymer with low dispersity (Ð = 1.09–1.22). Furthermore, the polymer maintained its characteristic lower critical solution temperature (LCST) behavior. More recently, reversible addition-fragmentation chain transfer (RAFT) polymerization was employed for the direct polymerization of biologically functional protecting group free peptides (one example is shown in Figure 8C).^[54] The resulting polymers, as well as high density peptide brushes, were characterized by low dispersity, pre-defined degree of polymerization and bioactivity.

Owing to high functional group tolerance, ROMP of protecting group free peptide monomers has been explored to generate bioactive materials of various types (Figure 8D).^[55] Initial investigations involved the generation of collections of peptide-functionalized monomers for ROMP in a systematic effort to establish functional group tolerance. These studies revealed that the amino acid sequence tolerance is broad outside of unprotected cysteine residues.^[17c] In turn, this led to the incorporation of complex biologically functional peptides including cell penetrating peptides,^[55] and potential therapeutic sequences previously not conceived (e.g. pro-apoptosis peptides).^[56] The polymers facilitated cell uptake, cytosolic distribution and bioactivity in disrupting mitochondrial membranes. In turn, we recently demonstrated a metal-free photoinduced reversible-deactivation radical polymerization (photo-RDRP) in both organic and aqueous phases to polymerize bioactive peptides including cell penetrating sequences (Figure 8E).^[57] Critically, polymers could be obtained under mild polymerization conditions using visible light, aqueous solution, and room temperature reactions.

Most intriguingly, the dense peptide brush polymer arrangement consistently enables protection of the peptide sidechain from degradation by proteases (Figure 9).^[55] This property appears general across peptide sequence and type of digestion enzyme, with some reliance on the degree of polymerization, with higher molecular weight homopolymers being optimal.^[55] Moreover, copolymerization with non-peptide based monomers causes degradation rates to increase as the peptide side chains become less densely arrayed.^[55] Therefore, this emergent and unexpected characteristic is attributed to the high density of these brush polymers in which multiple copies of peptides can be displayed in a protein-like polymer (PLP) globular structure wherein the peptides wrap the hydrophobic backbone (Figure 9A,B). In another application, brush polymer formulations of cell penetrating TAT peptides could be successfully used in the delivery of proteins to cells, while oligopeptides alone or oligopeptides displayed on nanoparticles did not (Figure 9C,D).^[58] All together, the recent advances made in the field of polymer chemistry allow the synthesis of well controlled peptide brush sequences which have the potential to overcome peptide limitations. This is of particular impact in the field of peptide therapeutics and bring peptides one step closer to clinical translation.

Figure 9.

Protein-Like Polymers (PLPs) prepared from peptide-modified norbornenes for display of proteolytically resistant peptides with functional qualities including acting as cell penetrating species for carrying proteins into cells. (A) In silico model of norbornenyl-peptide based brush polymers, or PLPs. (B) TAT peptides displayed as PLPs resist enzymatic degradation. Flow cytometry data showing that degraded material (peptides alone) do not enter cells, whereas the PLP-based TAT is protected from proteolysis and remains functional for cell uptake. (C) Configurations of a single peptide, a brush polymer, and a nanoparticle labelled with dye depicted by a yellow star. (D) The cytosolic delivery of Cre protein, monitored by a genomically-integrated fluorescence reporter is shown in the fluorescence microscopy images of HEK293T cells upon the treatment of Cre protein and the delivery systems. Scale bars are 20 μm. Figure adapted from Ref. [56] and [59]. Copyright 2014 American Chemical Society and 2019 Wiley-VCH Verlag GmbH & Co.

5. Summary and Outlook

The collections of brush polymers described herein represent a unique class of synthetic biomacromolecule. The polymers consistently show multivalent, length scale and stability advantages over the individual biomolecular oligomers that make up their side chains. Examples of cell uptake, and bioactivity being enhanced have arisen in non-obvious ways, especially in the case of the peptide work.^[56,57] Generalizable scaffolds for rapid formulation of biomolecular oligomers are increasingly sought after, where the basic monomers suffer short comings including a lack of desirable multivalency. Polymerization reactions to incorporate the biomolecules into brush polymer architectures, at high-densities via a graft-through approach, offer an efficient way of achieving this. These approaches are enabled by modern advancements in mild and functional group tolerant living polymerization methods coupled with solid phase synthetic approaches to complex, sequence defined biomolecules. These two synthetic approaches, taken together, represent two of the most efficient sets of reactions known. Simply, we take advantage of the fact that polymerization reactions are some of the best, most reproducible reactions in chemistry.^[59] In doing so, biomolecular oligomers can be rapidly formulated and engineered for effect.

The materials described herein draw on the considerable progress in the development of high yielding, scalable approaches to prepare synthetic biomolecules (i.e., oligonucleotides, oligosaccharides, and oligopeptides) for therapeutics, in self-assembled and nanoscale materials, and as tools in chemical biology. We believe that the recent progress in biomolecular brush polymers will not only expand the scope of therapeutic delivery systems, but also open the door to an unprecedented class of biomimetic materials with unique properties and applications.

Biographies

Wonmin Choi received his B.S.(2013) and M.S.(2015) degree in Chemistry from Seoul National University, Republic of Korea, under the supervision of Prof. Yan Lee. He is currently a Ph.D. student at Northwestern University under the auspices of Prof. Nathan C. Gianneschi. His research interests mainly focus on the development of novel peptide-based drug delivery platforms.

Nathan C. Gianneschi received his B.Sc-(Hons) in Chemistry at the University of Adelaide, Australia (1999) and his Ph.D at Northwestern University (2005). After graduation he conducted his Postdoctoral Fellowship at The Scripps Research Institute where he was a Dow Chemical Company American Australian Association Fellow. He is currently Jacob & Rosaline Cohn Professor of Chemistry, Materials Science & Engineering, Biomedical Engineering and Pharmacology at Northwestern University. His work is broadly in the area of multifunctional polymeric materials with relevance in biomedical applications. In addition, he leads a basic research program focused on nanoscale materials design, synthesis and characterization.