One hundred years ago Hermann Staudinger was strongly criticized by his scientific peers for his macromolecular hypothesis, but today it is hard to imagine a world without polymers. His hypothesis ...described polymers as macromolecules composed of large numbers of structural units connected by covalent bonds. In the 1990s the concept of supramolecular polymers emerged in the scientific literature as discrete entities of large molar mass comparable to that of classical polymers but built through non-covalent bonds among monomers. Supramolecular polymers exist in biological systems, and potentially blend the physical properties of covalent polymers with unique features such as high degrees of internal order within the polymeric structure, defined shapes, and novel dynamics. This trend article provides a summary of seminal contributions in supramolecular polymerization and provides recent examples from the Stupp laboratory to demonstrate the potential applications of an exciting class of materials composed fully or partially of supramolecular polymers. In closing, we provide our perspective on future opportunities provided by this field at the onset of a second century of polymers. It is our objective here to demonstrate that this second century could be as prosperous, if not more so, than the preceding one.
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The role of nanoparticles in cancer medicine is vast with debate still surrounding the distinction between therapeutic efficacy of actively targeted nanoparticles versus passively targeted systems ...for drug delivery. While it is commonly accepted that methodologies that result in homing a high concentration of drug loaded nanoparticles to the tumor is beneficial, the role of intracellular trafficking of these nanoparticles in dictating the overall therapeutic outcome remains unresolved. Herein we demonstrate that the therapeutic outcome of drug loaded nanoparticles is governed beyond simply enabling nanoparticle internalization in cells. Using two model polymeric nanoparticles, one decorated with the GE11 peptide for active targeting of the epidermal growth factor receptor (EGFR) and the other without, we demonstrate that EGFR mediated intracellular internalization results in an enhanced therapeutic effect compared to the nontargeted formulation. Our findings demonstrate that the intracellular destination of nanoparticles beyond its ability to internalize is an important parameter that has to be accounted for in the design of targeted drug delivery systems.
This Letter describes the use of CdSe quantum dots (QDs) as photocatalysts for photoinduced electron transfer reversible addition–fragmentation chain transfer (PET-RAFT) polymerization of a series of ...aqueous acrylamides and acrylates. The high colloidal solubility and photostability of these QDs allowed polymerization to occur with high efficiency (>90% conversion in 2.5 h), low dispersity (PDI < 1.1), and ultralow catalyst loading (<0.5 ppm). The use of protein concentrators enabled the removal of the photocatalyst from the polymer and monomer with tolerable metal contamination (8.41 ug/g). These isolated QDs could be recycled for four separate polymerizations without a significant decrease in efficiency. By changing the pore size of the protein concentrators, the QDs and polymer could be separated from the remaining monomer, allowing for the synthesis of block copolymers using a single batch of QDs with minimal purification steps and demonstrating the fidelity of chain ends.
Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of ...enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases.
The size and shape of polymer materials is becoming an increasingly important property in accessing new functions and applications of nano‐/microparticles in many scientific fields. New synthetic ...methods have allowed unprecedented capability for the facile fabrication of anisotropic and shape‐defined nanomaterials. Bottom‐up approaches including: emulsion polymerization techniques, amphiphile self‐assembly, and polymerization‐induced self‐assembly, can lead to polymer particles with precise dimensions in the nanoscale. Top‐down methods such as lithographic templating, and 3D printing, have increased the access to unique particle shapes. In this review, these recent developments are appraised and contrasted, with future research directions providing that focus on biomedical applications. Finally, the opportunity available for synergistic combinations of top‐down and bottom‐up fabrication approaches in realizing previously unattainable architectures and material properties is highlighted.
The current state of the art in both bottom‐up and top‐down synthetic approaches for controlling nanomaterial properties for biomedical applications is highlighted. Recent examples are explored, which combine these synthetic strategies, and an insight into how synergistic combinations of bottom‐up and top‐down approaches can result in the realization of unique material properties is provided.
Supramolecular-covalent hybrid polymers have been shown to be interesting systems to generate robotic functions in soft materials in response to external stimuli. In recent work supramolecular ...components were found to enhance the speed of reversible bending deformations and locomotion when exposed to light. The role of morphology in the supramolecular phases integrated into these hybrid materials remains unclear. We report here on supramolecular-covalent hybrid materials that incorporate either high-aspect-ratio peptide amphiphile (PA) ribbons and fibers, or low-aspect-ratio spherical peptide amphiphile micelles into photo-active spiropyran polymeric matrices. We found that the high-aspect-ratio morphologies not only play a significant role in providing mechanical reinforcement to the matrix but also enhance photo-actuation for both light driven volumetric contraction and expansion of spiropyran hydrogels. Molecular dynamics simulations indicate that water within the high-aspect-ratio supramolecular polymers exhibits a faster draining rate as compared to those in spherical micelles, which suggests that the high-aspect-ratio supramolecular polymers effectively facilitate the transport of trapped water molecules by functioning as channels and therefore enhancing actuation of the hybrid system. Our simulations provide a useful strategy for the design of new functional hybrid architectures and materials with the aim of accelerating response and enhancing actuation by facilitating water diffusion at the nanoscopic level.
Supramolecular-covalent hybrid spiropyran hydrogels are developed to generate robotic functions in response to light. The morphology of supramolecular phases is found to play a critical role in mechanical photo-actuation of these hybrid hydrogels.
Herein, we report the photoinitiated polymerization‐induced self‐assembly (photo‐PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one‐pot synthetic approach ...yielded micellar nanoparticles at high concentrations and at scale (150 mg mL−1) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide‐functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo‐PISA in the large‐scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.
Polymerization‐induced self‐assembly enables the at scale synthesis of nanoparticles with a high‐density display of peptide, tunable particle size, and tunable peptide loadings. The resulting peptide brush polymer nanoparticles exhibit enhanced stability, and cell uptake efficiency and efficacy in comparison with their peptide analogues, highlighting the potential of these peptide–polymer amphiphiles as peptide delivery systems.
Reversible addition‐fragmentation chain transfer (RAFT) polymerization has proven itself as a powerful polymerization technique affording facile control of molecular weight, molecular weight ...distribution, architecture, and chain end groups ‐ while maintaining a high level of tolerance for solvent and monomer functional groups. RAFT is highly suited to water as a polymerization solvent, with aqueous RAFT now utilized for applications such as controlled synthesis of ultra‐high molecular weight polymers, polymerization induced self‐assembly, and biocompatible polymerizations, among others. Water as a solvent represents a non‐toxic, cheap, and environmentally friendly alternative to organic solvents traditionally utilized for polymerizations. This, coupled with the benefits of RAFT polymerization, makes for a powerful combination in polymer science. This perspective provides a historical account of the initial developments of aqueous RAFT polymerization at the University of Southern Mississippi from the McCormick Research Group, details practical considerations for conducting aqueous RAFT polymerizations, and highlights some of the recent advances aqueous RAFT polymerization can provide. Finally, some of the future opportunities that this versatile polymerization technique in an aqueous environment can offer are discussed, and it is anticipated that the aqueous RAFT polymerization field will continue to realize these, and other exciting opportunities into the future.
This perspective provides a historical account of the initial developments of aqueous reversible addition‐fragmentation chain transfer (RAFT) polymerization at the University of Southern Mississippi from the McCormick Research Group, details practical considerations for conducting aqueous RAFT polymerizations, and highlights some of the recent advances aqueous RAFT polymerization has afforded.
Melanin is a ubiquitous natural pigment found in a diverse array of organisms. Allomelanin is a class of nitrogen-free melanin often found in fungi. Herein, we find artificial allomelanin analogues ...exhibit high intrinsic microporosity and describe an approach for further increasing and tuning that porosity. Notably, the synthetic method involves an oxidative polymerization of 1,8-DHN in water, negating the need for multiple complex templating steps and avoiding expensive or complex chemical precursors. The well-defined morphologies of these nanomaterials were elucidated by a combination of electron microscopy and scattering methods, yielding to high-resolution 3D reconstruction based on small-angle X-ray scattering (SAXS) results. Synthetic allomelanin nanoparticles exhibit high BET areas, up to 860 m2/g, and are capable of ammonia capture up to 17.0 mmol/g at 1 bar. In addition, these nanomaterials can adsorb nerve agent simulants in solution and as a coating on fabrics with high breathability where they prevent breakthrough. We also confirmed that naturally derived fungal melanin can adsorb nerve gas simulants in solution efficiently despite lower porosity than synthetic analogues. Our approach inspires further analysis of yet to be discovered biological materials of this class where melanins with intrinsic microporosity may be linked to evolutionary advantages in relevant organisms and may in turn inspire the design of new high surface area materials.
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