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Peptide-brush polymers (PBPs), wherein every side-chain of the polymers is peptidic, represent a new class of proteomimetic with unusually high proteolytic resistance while maintaining bioactivity. Here, we sought to determine the origin of this behavior and to assess its generality via a combined theory and experimental approach. A series of PBPs with various polymer backbone structures were prepared and examined for their proteolytic stability and bioactivity. We discovered that an increase in the hydrophobicity of the polymer backbones is predictive of an elevation in proteolytic stability of the side-chain peptides. Computer simulations, together with small-angle X-ray scattering (SAXS) analysis, revealed globular morphologies for these polymers, in which pendant peptides condense around hydrophobic synthetic polymer backbones driven by the hydrophobic effect. As the hydrophobicity of the polymer backbones increases, the extent of solvent exposure of peptide cleavage sites decreases, reducing their accessibility to proteolytic enzymes. This study provides insight into the important factors driving PBP aqueous-phase structures to behave as globular, synthetic polymer-based proteomimetics., This study sheds light on the origin of peptide-brush polymers as globular proteomimetics and protein-like polymers by examining them for their structure and stability.

We report a novel glycan array architecture that binds the mannose-specific glycan binding protein, concanavalin A (ConA), with sub-femtomolar avidity. A new radical photopolymerization developed specifically for this application combines the grafted-from thiol-(meth)acrylate polymerization with thiol-ene chemistry to graft glycans to the growing polymer brushes. The propagation of the brushes was studied by carrying out this grafted-to/grafted-from radical photopolymerization (GTGFRP) at >400 different conditions using hypersurface photolithography, a printing strategy that substantially accelerates reaction discovery and optimization on surfaces. The effect of brush height and the grafting density of mannosides on the binding of ConA to the brushes was studied systematically, and we found that multivalent and cooperative binding account for the unprecedented sensitivity of the GTGFRP brushes. This study further demonstrates the ease with which new chemistry can be tailored for an application as a result of the advantages of hypersurface photolithography.

High catalytic activity and substrate specificity make enzymes a rich source of inspiration for catalyst development. Co-opting the advantages of natural materials while tuning them to a modified f...

Melanin is ubiquitous in living organisms across different biological kingdoms of life, making it an important, natural biomaterial. Its presence in nature from microorganisms to higher animals and plants is attributed to the many functions of melanin, including pigmentation, radical scavenging, radiation protection, and thermal regulation. Generally, melanin is classified into five types-eumelanin, pheomelanin, neuromelanin, allomelanin, and pyomelanin-based on the various chemical precursors used in their biosynthesis. Despite its long history of study, the exact chemical makeup of melanin remains unclear, and it moreover has an inherent diversity and complexity of chemical structure, likely including many functions and properties that remain to be identified. Synthetic mimics have begun to play a broader role in unraveling structure and function relationships of natural melanins. In the past decade, polydopamine, which has served as the conventional form of synthetic eumelanin, has dominated the literature on melanin-based materials, while the synthetic analogues of other melanins have received far less attention. In this perspective, we will discuss the synthesis of melanin materials with a special focus beyond polydopamine. We will emphasize efforts to elucidate biosynthetic pathways and structural characterization approaches that can be harnessed to interrogate specific structure-function relationships, including electron paramagnetic resonance (EPR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. We believe that this timely Perspective will introduce this class of biopolymer to the broader chemistry community, where we hope to stimulate new opportunities in novel, melanin-based poly-functional synthetic materials.

International audience; Interpenetration of two or more sublattices is common among many metal–organic frameworks (MOFs). Herein, we study the evolution of one zirconium cluster-based, 3,8-connected MOF from its non-interpenetrated (NU-1200) to interpenetrated (STA-26) isomer. We observe this transient catenation process indirectly using ensemble methods, such as nitrogen porosimetry and X-ray diffraction, and directly, using high-resolution transmission electron microscopy. The approach detailed here will serve as a template for other researchers to monitor the interpenetration of their MOF samples at the bulk and single-particle limits. We investigate the mechanical stability of both lattices experimentally by pressurized in situ X-ray diffraction and nanoindentation as well as computationally with density functional theory calculations. Both lines of study reveal that STA-26 is considerably more mechanically stable than NU-1200. We conclude this study by demonstrating the potential of these MOFs and their mixed phases for the capture of gaseous n-hexane, used as a structural mimic for the chemical warfare agent sulfur mustard gas.

Structurally colored supraparticles, formed from dispersed nanoparticle building blocks through self-assembly, have tremendous potential for applications in displays, coatings, paints, inks, and co...

Emergent quantum phenomena in electronically coupled two-dimensional heterostructures are central to next-generation optical, electronic, and quantum information applications. Tailoring electronic band gaps in coupled heterostructures would permit control of such phenomena and is the subject of significant research interest. Two-dimensional polymers (2DPs) offer a compelling route to tailored band structures through the selection of molecular constituents. However, despite the promise of synthetic flexibility and electronic design, fabrication of 2DPs that form electronically coupled 2D heterostructures remains an outstanding challenge. Here, we report the rational design and optimized synthesis of electronically coupled semiconducting 2DP/2D transition metal dichalcogenide van der Waals heterostructures, demonstrate direct exfoliation of the highly crystalline and oriented 2DP films down to a few nanometers, and present the first thickness-dependent study of 2DP/MoS2 heterostructures. Control over the 2DP layers reveals enhancement of the 2DP photoluminescence by two orders of magnitude in ultrathin sheets and an unexpected thickness-dependent modulation of the ultrafast excited state dynamics in the 2DP/MoS2 heterostructure. These results provide fundamental insight into the electronic structure of 2DPs and present a route to tune emergent quantum phenomena in 2DP hybrid van der Waals heterostructures.

We report aqueous-phase Ring-Opening Metathesis Polymerization-Induced Self-Assembly (ROMPISA) for forming well-defined micellar polymer nanoparticles at room temperature and high solids concentration (20 w/w%). This is achieved with a new polymerization initiator, in the form of a water-soluble cationic Hoveyda-Grubbs second generation catalyst. This reaction was used in water to produce diblock copolymers from norbornenyl monomers, which then self-assemble into myriad nanostructure morphologies for which a phase diagram was constructed. Additionally, the living nature of the polymerization initiated by the aqueous initiator was confirmed, as shown by kinetic evaluation under mild conditions in water.

Recent reports suggest that next-generation hair dyes might take inspiration from the natural pigment melanin. In humans, melanin imparts color to hair and skin and acts as a natural sunscreen and ...

The encapsulation of enzymes within porous materials has shown great promise, not only in protecting the enzymes from denaturation under nonbiological environments, but also, in some cases, in facilitating their enzymatic reaction rates at favorable reaction conditions. While a number of hypotheses have been developed to explain this phenomenon, the detailed structural changes of the enzymes upon encapsulation within the porous material, which are closely related to their activity, remain largely elusive. Herein, the structural change of cytochrome c (Cyt c) upon encapsulation within a hierarchical metal-organic framework, NU-1000, is investigated through a combination of experimental and computational methods, such as electron paramagnetic resonance, solid-state ultraviolet-visible spectroscopy, and all-atom explicit solvent molecular dynamics simulations. The enhanced catalytic performance of Cyt c after being encapsulated within NU-1000 is supported by the physical and in silico observations of a change around the heme ferric active center.

Metal-organic frameworks (MOFs) are hybrid materials composed of metal ions and organic linkers featuring high porosity, crystallinity, and chemical tunability at multiple length scales. A recent advancement in transmission electron microscopy (TEM) and its direct application to MOF structure-property relationships have changed how we consider rational MOF design and development. Herein, we provide a perspective on TEM studies of MOFs and highlight the utilization of state-of-the-art TEM technologies to explore dynamic MOF processes and host-guest interactions. Additionally, we provide thoughts on what the future holds for TEM in the study of MOFs.

We report the synthesis of a degradable polyphosphoramidate via ring-opening metathesis polymerization (ROMP) with the Grubbs initiator (IMesH2)(C5H5N)2(Cl)2Ru═CHPh. Controlled ROMP of a low ring s...

This article addresses recent advances in liquid phase transmission electron microscopy (LPTEM) for studying nanoscale synthetic processes of carbon-based materials that are independent of the electron beam—those driven by nonradiolytic chemical or thermal reactions. In particular, we focus on chemical/physical formations and the assembly of nanostructures composed of organic monomers/polymers, peptides/DNA, and biominerals. The synthesis of carbon-based nanomaterials generally only occurs at specific conditions, which cannot be mimicked by aqueous solution radiolysis. Carbon-based structures themselves are also acutely sensitive to the damaging effects of the irradiating beam, which make studying their synthesis using LPTEM a unique challenge that is possible when beam effects can be quantified and mitigated. With new direct sensing, high frame-rate cameras, and advances in liquid cell holder designs, combined with a growing understanding of irradiation effects and proper experimental controls, microscopists have been able to make strides in observing traditionally problematic carbon-based materials under conditions where synthesis can be controlled, and imaged free from beam effects, or with beam effects quantified and accounted for. These materials systems and LPTEM experimental techniques are discussed, focusing on nonradiolytic chemical and physical transformations relevant to materials synthesis.

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.

Melanins are a family of heterogeneous biopolymers found ubiquitously across plant, animal, bacterial, and fungal kingdoms where they act variously as pigments and as radiation protection agents. There exist five multifunctional yet structurally and biosynthetically incompletely understood varieties of melanin: eumelanin, neuromelanin, pyomelanin, allomelanin, and pheomelanin. Although eumelanin and allomelanin have been the focus of most radiation protection studies to date, some research suggests that pheomelanin has a better absorption coefficient for X-rays than eumelanin. We reasoned that if a selenium enriched melanin existed, it would be a better X-ray protector than the sulfur-containing pheomelanin because the X-ray absorption coefficient is proportional to the fourth power of the atomic number (Z). Notably, selenium is an essential micronutrient, with the amino acid selenocysteine being genetically encoded in 25 natural human proteins. Therefore, we hypothesize that selenomelanin exists in nature, where it provides superior ionizing radiation protection to organisms compared to known melanins. Here we introduce this novel selenium analogue of pheomelanin through chemical and biosynthetic routes using selenocystine as a feedstock. The resulting selenomelanin is a structural mimic of pheomelanin. We found selenomelanin effectively prevented neonatal human epidermal keratinocytes (NHEK) from G2/M phase arrest under high-dose X-ray irradiation. Provocatively, this beneficial role of selenomelanin points to it as a sixth variety of yet to be discovered natural melanin.

Human hair is naturally colored by melanin pigments, which afford myriad colors from black, to brown, to red depending on the chemical structures and specific blends. In recent decades, synthetic efforts have centered on dopamine oxidation to polydopamine, an effective eumelanin similar to the one found in humans. To date, only a few attempts at polydopamine deposition on human hair have been reported, and their translation to widespread usage and potential commercialization is still hampered by the harsh conditions employed. We reasoned that novel, mild, biocompatible approaches could be developed to establish a metal-free route to tunable, nature-inspired, long-lasting coloration of human hair. Herein, we describe synthetic and formulation routes to achieving this goal and show efficacy on a variety of human hair samples via multiple spectroscopic and imaging techniques. Owing to the mild and inexpensive conditions employed, this novel approach has the potential to replace classical harsh hair dyeing conditions that have raised concerns for several decades due to their potential toxicity., Synthetic melanin nanoparticle coatings on hair surfaces successfully reverse the appearance of melanin loss and hair whitening and provides a novel biomimetic and nontoxic approach to hair dyeing.

Zr6-based metal-organic frameworks (MOFs) with tetratopic organic linkers have been extensively investigated owing to their versatile structural tunability. While diverse topologies and polymorphism in the resulting MOFs are often encountered with tetratopic linkers and Zr6 nodes, reports on phase transitions within these systems are rare. Thus, we have a limited understanding of polymorph transformations, hindering the rational development of pure phase materials. In this study, a phase transition from a microporous MOF, scu-NU-906, to a mesoporous MOF, csq-NU-1008, was discovered and monitored through in situ variable temperature liquid-cell transmission electron microscopy (VT-LCTEM), high-resolution transmission electron microscopy (HRTEM), and in situ variable temperature powder X-ray diffraction (VT-PXRD). It was found that the microporous- to-mesoporous transformation in the presence of formic acid occurs via a concomitant dissolution-reprecipitation process.

The intriguing catalytic properties of cerium-based materials have motivated the development of Ce-based metal–organic frameworks (MOFs). However, the controlled crystallization of Ce MOFs remains nascent due to complications with the high reduction potential of Ce4+ species. Modulators offer a route in other well-studied coordination networks to slow down crystallization processes to allow for corrective, uniform crystal growth. Herein, we report an investigation of modulator identity and concentration on the synthesis of a Ce-UiO-type MOF with 2,6-naphthalenedicarboxylic acid (NDC) as a linker. At low concentrations using both benzoic acid and trifluoroacetic acid, we observed a mononuclear Ce3+ MOF (NU-350) through single-crystal X-ray diffraction studies. Higher modulator concentrations yielded pure-phase Ce-UiO-NDC, with uniform particle sizes observed with utilizing benzoic acid as a modulator. Moreover, we demonstrated the transferability of this synthesis through the pure-phase synthesis of Ce-UiO-66 with benzoic acid as a modulator. High-resolution transmission electron microscopy showed a single crystalline domain within Ce-UiO-NDC.

In this report, we explore the internal structural features of polyMOFs consisting of equal mass ratios of metal-coordinating poly(benzenedicarboxylic acid) blocks and non-coordinating poly(ethylene glycol) (PEG) blocks. The studies reveal alternating lamellae of metal-rich, crystalline regions and metal-deficient non-crystalline polymer, which span the length of hundreds of nanometers. Polymers consisting of random PEG blocks, PEG end-blocks, or non-coordinating poly(cyclooctadiene) (COD) show similar alternation of metal-rich and metal-deficient regions, indicating a universal self-assembly mechanism. A variety of techniques were employed to interrogate the internal structure of the polyMOFs, including transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and small-angle synchrotron X-ray scattering (SAXS). Independent of the copolymer architecture or composition, the internal structure of the polyMOF crystals showed similar lamellar self-assembly at single-nanometer length scales., In this report, we explore the internal structural features of polyMOFs consisting of equal mass ratios of metal-coordinating poly(benzenedicarboxylic acid) blocks and non-coordinating poly(ethylene glycol) (PEG) blocks.

Isoreticular synthesis is a powerful tool to enhance specific attributes of a metal-organic framework (MOF). While the isoreticular expansion of MOF structure are prevalent in the literature, the compression of a topology holds great promise for separations due to the contracted pore apertures and/or cavities. Herein, we report the synthesis, characterization and Xe/Kr separation capability of a new Zr-based MOF, NU-1106, connected by the tetratopic linker 1,3,6,8-pyrene tetracarboxylate, which exhibits a compressed ftw topology compared to the extended ones reported previously. NU-1106 showed selective uptake of Xenon over Krypton, providing the potential for use for separations.

In this paper, we report the preparation of paclitaxel-terminated peptide brush polymers wherein cell uptake and toxicity are tunable based on peptide sequence. Synthesis was enabled using a new paclitaxel-containing chain termination agent for ring-opening metathesis polymerization (ROMP). Critically, reverse phase HPLC could be used to efficiently separate peptide brush polymers consisting of one fluorophore and one terminal paclitaxel from crude polymer mixtures. These purified terminally-modified polymers showed greater potency than the original mixtures. Drug-terminated peptide brush polymers carrying positive charges exhibited enhanced cell uptake and cytotoxicity as compared to their neutral and negatively charged analogues.

Crystalline, electrically conductive, and intrinsically porous materials are rare. Layered two-dimensional (2D) metal–organic frameworks (MOFs) break this trend. They are porous crystals that exhibit high electrical conductivity and are novel platforms for studying fundamentals of electricity and magnetism in two dimensions. Despite demonstrated applications, electrical transport in these remains poorly understood because of a lack of single crystal studies. Here, studies of single crystals of two 2D MOFs, Ni3(HITP)2 and Cu3(HHTP)2, uncover critical insights into their structure and transport. Conductivity measurements down to 0.3 K suggest metallicity for mesoscopic single crystals of Ni3(HITP)2, which contrasts with apparent activated conductivity for polycrystalline films. Microscopy studies further reveal that these MOFs are not isostructural as previously reported. Notably, single rods exhibit conductivities up to 150 S/cm, which persist even after prolonged exposure to ambient conditions. These single crystal studies confirm that 2D MOFs hold promise as molecularly tunable platforms for fundamental science and applications where porosity and conductivity are critical., A single crystal conductive metal−organic frameworks device and its metallic conduction.

Recently, we presented a strategy for packaging peptides as side-chains in high-density brush polymers. For this globular protein-like polymer (PLP) formulation, therapeutic peptides were shown to resist proteolytic degradation, enter cells efficiently and maintain biological function. In this paper, we establish the role charge plays in dictating the cellular uptake of these peptide formulations, finding that peptides with a net positive charge will enter cells when polymerized, while those formed from anionic or neutral peptides remain outside of cells. Given these findings, we explored whether cellular uptake could be selectively induced by a stimulus. In our design, a cationic peptide is appended to a sequence of charge-neutralizing anionic amino acids through stimuli-responsive cleavable linkers. As a proof-of-concept study, we tested this strategy with two different classes of stimuli, exogenous UV light and an enzyme (a matrix metalloproteinase) associated with the inflammatory response. The key finding is that these materials enter cells only when acted upon by the stimulus. This approach makes it possible to achieve delivery of the polymers, therapeutic peptides or an appended cargo into cells in response to an appropriate stimulus.

Self-assembling peptides (SAPs), which form hydrogels through physical cross-linking of soluble structures, are an intriguing class of materials that have been applied as tissue engineering scaffolds and drug delivery vehicles. For feasible application of these tissue mimetics via minimally invasive delivery, their bulk mechanical properties must be compatible with current delivery strategies. However, injectable SAPs which possess shear-thinning capacity, as well as the ability to reassemble after cessation of shearing can be technically challenging to generate. Many SAPs either clog the high-gauge needle/catheter at high concentration during delivery or are incapable of reassembly following delivery. In this chapter, we provide a detailed protocol for topological control of enzyme-responsive peptide-based hydrogels that enable the user to access both advantages. These materials are formulated as sterically constrained cyclic peptide progelators to temporarily disrupt self-assembly during injection-based delivery, which avoids issues with clogging of needles and catheters as well as nearby vasculature. Proteolytic cleavage by enzymes produced at the target tissue induces progelator linearization and hydrogelation. The scope of this approach is demonstrated by their ability to flow through a catheter without clogging and activated gelation upon exposure to target enzymes.

The synthesis of periodic two-dimensional (2D) polymers and characterization of their optoelectronic behaviors are challenges at the forefront of polymer chemistry and materials science. Recently, we showed that layered 2D polymers known as 2D covalent organic frameworks (COFs) can be synthesized as single crystals by preparing COF particles as colloidal suspensions. Here we expand this approach from the condensation of boronic acids and catechols to the dehydrative trimerization of polyboronic acids. The resulting boroxine-linked colloids are the next class of 2D COFs to be obtained as single-crystalline particles, as demonstrated here for four 2D COFs and one 3D COF. Colloidal stabilization enables detailed structural analysis by synchrotron X-ray diffraction and high-resolution transmission electron microscopy. Solution fluorescence spectroscopy revealed that the COF crystallites are highly emissive compared to their respective monomer solutions. Excitation-emission matrix fluorescence spectroscopy indicated that the origin of this enhanced emission can be attributed to through-space communication of chromophores between COF sheets. These observations will motivate the development of colloidal COF systems as a platform to organize functional aromatic systems into precise and predictable assemblies with emergent properties.

Two-dimensional covalent organic frameworks (2D COFs) are composed of structurally precise, permanently porous, layered polymer sheets. 2D COFs have traditionally been synthesized as polycrystalline aggregates with small crystalline domains. Only recently have a small number of 2D COFs been obtained as single crystals, which were prepared by a seeded growth approach via the slow introduction of monomers, which favored particle growth over nucleation. However, these procedures are slow and operationally difficult, making it desirable to develop polymerization methods that do not require the continuous addition of reactants over days or weeks. Here, we achieve the rapid growth of boronate ester-linked COFs by chemically suppressing nucleation via addition of an excess of a monofunctional competitor, 4-tert-butylcatechol (TCAT), into the polymerization. In situ X-ray scattering measurements show that TCAT suppresses colloid nucleation, which enables seeded growth polymerizations in the presence of high monomer concentrations. Kinetic Monte Carlo simulations reveal that TCAT limits oligomers to sizes below the critical nucleus size and that in-plane expansion is restricted compared to out-of-plane oriented attachment of oligomers. The simulations are consistent with transmission electron micrographs, which show that the particles grow predominantly in the stacking direction. This mechanistic insight into the role of the modulators in 2D polymerizations enables the size and aspect ratio of COF colloids to be controlled under operationally simple conditions. This chemically controlled growth strategy will accelerate the discovery and exploration of COF materials and their emergent properties., The addition of a monofunctional competitor enables chemical control over nucleation and results in anisotropic growth of 2D COF colloids.

Harnessing metal-free photoinduced reversible-deactivation radical polymerization (photo-RDRP) in organic and aqueous phases, we report a synthetic approach to enzyme-responsive and pro-apoptotic peptide brush polymers. Thermolysin-responsive peptide based polymeric amphiphiles assembled into spherical micellar nanoparticles that undergo a morphology transition to worm-like micelles upon enzyme-triggered cleavage of coronal peptide sidechains. Moreover, pro-apoptotic polypeptide brushes show enhanced cell uptake over individual peptide chains of the same sequence, resulting in a significant increase in cytotoxicity to cancer cells. Critically, increased grafting density of pro-apoptotic peptides on brush polymers correlates with increased uptake efficiency and concurrently, cytotoxicity. The mild synthetic conditions afforded by photo-RDRP, make it possible to access well-defined peptide-based polymer bioconjugate structures with tunable bioactivity.

The scarcity of effective means to deliver functional proteins to living cells is a central problem in biotechnology and medicine. Herein, we report the efficient delivery of an active DNA-modifying enzyme to human stem cells through high-density cell penetrating peptide brush polymers. Cre recombinase is mixed with a fluorophore-tagged polymer carrier and then applied directly to induced pluripotent stem cells or HEK293T cells. This results in efficient delivery of Cre protein as measured by activation of a genomically integrated Cre-mediated recombination reporter. We observed that brush polymer formulations utilizing cell penetrating peptides promoted Cre delivery but oligopeptides alone or oligopeptides displayed on nanoparticles did not. Overall, we report the efficient delivery of a genome-modifying enzyme to stem cells that may be generalizable to other, difficult-to-transduce cell types.

Allomelanin is a type of nitrogen-free melanin most commonly found in fungi. Its existence enhances resistance of the organisms to environmental damage and helps fungi survive harsh radiation conditions such as those found on spacecraft and inside contaminated nuclear power plants. We report the preparation and characterization of artificial allomelanin nanoparticles (AMNPs) via oxidative oligomerization of 1,8-dihydroxynaphthalene (1,8-DHN). We describe the resulting morphological and size control of AMNPs and demonstrate that they are radical scavengers. Finally, we show that AMNPs are taken up by neonatal human epidermal keratinocytes and packaged into perinuclear caps where they quench reactive oxygen species generated following UV exposure.

In this paper, experiment and simulation were combined to provide a view of the molecular rearrangements underlying the equilibrium and nonequilibrium transitions occurring in stimuli-responsive block copolymer amphiphile self-assemblies. Three block copolymer amphiphiles were prepared, each consisting of a hydrophilic peptide brush, responsive to proteolytic enzymes, and containing one of three possible hydrophobic blocks: (1) poly(ethyl acrylate), (2) poly(styrene), or (3) poly(lauryl acrylate). When assembled, they generate three spherical micelles each responsive to the addition of the bacterial protease, thermolysin. We found core-block-dependent phase transitions in response to the hydrophilic block being truncated by the stimulus. In one example, we found an unexpected, well-defined, pathway-dependent spherical micelle to vesicle phase transition induced by enzymatic stimulus.

Perfluorocarbon emulsion nanodroplets containing iron oxide nanoparticles (IONPs) within their inner perfluorohexane (PFH) core were prepared to investigate potential use as an acoustically activatable ultrasound contrast agent, with the hypothesis that incorporation of IONPs into the fluorous phase of a liquid perfluorocarbon emulsion would potentiate acoustic vaporization. IONPs with an oleic acid (OA) hydrophobic coating were synthesized through chemical co-precipitation. To suspend IONP in PFH, OA was exchanged with perfluorononanoic acid (PFNA) via ligand exchange to yield fluorophilic PFNA-coated IONPs (PFNA-IONPs). Suspensions with various amounts of PFNA-IONPs (0–15% w/v) in PFH were emulsified in saline by sonication, using 5% (w/v) egg yolk phospholipid as an emulsifier. PFNA-IONPs were characterized with transmission electron microscopy (TEM), transmission electron cryomicroscopy (cryoTEM), and thermogravimetric analysis (TGA) with Fourier transform infrared spectroscopy (FTIR). IONP were between 5 and 10 nm in diameter as measured by electron microscopy, and hydrodynamic size of the PFH nanodroplets were 150 to 230 nm as measured by dynamic light scattering (DLS). Acoustic droplet vaporization of PFH nanodroplets (PFH-NDs) was induced using conversion pulses (100 cycle at 1.1 MHz and 50% duty cycle) provided by a focused ultrasound transducer, and formed microbubbles were imaged using a clinical ultrasound scanner. The acoustic pressure threshold needed for PFH-NDs vaporization decreased with increasing temperature and IONP content. PFH-NDs containing 5% w/v IONP converted to microbubbles at 42 °C at 2.18 MI, which is just above the exposure limits of 1.9 MI allowed by the FDA for clinical ultrasound scanners, whereas 10 and 15% emulsion vaporized at 1.87 and 1.24 MI, respectively. Furthermore, 5% IONP-loaded PFH-NDs injected intravenously into melanoma-bearing mice at a dose of 120 mg PFH/kg, converted into detectable microbubbles in vivo 5 h, but not shortly after injection, indicating that this technique detects NDs accumulated in tumors.

The surface charge densities, apparent equilibrium binding constants, and free energies of binding of nickel ions to supported and suspended lipid membranes prepared from POPC and two types of lipopolysaccharide (LPS) are reported. Second- and third-order nonlinear optical mixing shows that rough LPS (rLPS)-incorporated bilayers carry the highest charge density and provide the most binding sites for nickel ions while LPS-free bilayers exhibit the lowest charge density and fewest binding sites. Ni2+ binding is almost fully reversible at low concentrations but less so at higher Ni2+ concentrations. Ni2+ adsorption isotherms exhibit hysteresis loops. The role of interfacial depth on the observed second harmonic generation (SHG) responses is discussed in the context of complementary dynamic light scattering, X-ray spectroscopy, and cryogenic transmission electron microscopy experiments. The latter reveal considerable Ni2+-induced structural deformations to the bacterial membrane models containing the short, O-antigen-free rLPS, consistent with complex formation on the vesicle surfaces that involve Ni2+ ions and carboxylate groups in the inner core of rLPS. In contrast, Ni2+ ion complexation to the charged groups (phosphates and carboxylate) of the considerably longer O-antigen units in sLPS appears to protect the phospholipid backbone against metal binding and thus preserve the vesicle structure.

Over the past decade, the field of polymer-oligonucleotide nanomaterials has flourished because of the development of synthetic techniques, particularly living polymerization technologies, which provide access to polymers with well-defined architectures, precise molecular weights, and terminal or side-chain functionalities. Various "living" polymerization methods have empowered chemists with the ability to prepare functional polymer-oligonucleotide conjugates yielding a library of architectures, including linear diblock, comb, star, hyperbranched star, and gel morphologies. Since oligonucleotides are hydrophilic and synthetic polymers can be tailored with hydrophobicity, these amphiphilic polymer-oligonucleotide conjugates are capable of self-assembling into nanostructures with different shapes, leading to many high-value-added biomedical applications, such as drug delivery systems, gene regulation, and 3D-bioprinting. This review aims to highlight the main living polymerization approaches to polymer-oligonucleotide conjugates, including ring-opening metathesis polymerization, atom transfer radical polymerization (ATRP), reversible addition-fragmentation transfer polymerization (RAFT), and ring-opening polymerization of cyclic esters and N-carboxyanhydride. The self-assembly properties and resulting applications of polymer-DNA hybrid materials are highlighted as well.

Injectable biopolymer hydrogels have gained attention for use as scaffolds to promote cardiac function and prevent negative left ventricular (LV) remodeling post-myocardial infarction (MI). However, most hydrogels tested in preclinical studies are not candidates for minimally invasive catheter delivery due to excess material viscosity, rapid gelation times, and/or concerns regarding hemocompatibility and potential for embolism. We describe a platform technology for progelator materials formulated as sterically constrained cyclic peptides which flow freely for low resistance injection, and rapidly assemble into hydrogels when linearized by disease-associated enzymes. Their utility in vivo is demonstrated by their ability to flow through a syringe and gel at the site of MI in rat models. Additionally, synthetic functionalization enables these materials to flow through a cardiac injection catheter without clogging, without compromising hemocompatibility or cytotoxicity. These studies set the stage for the development of structurally dynamic biomaterials for therapeutic hydrogel delivery to the MI., Injectable hydrogels have gained significant interest; yet, due to high viscosity, many are unsuitable for catheter delivery. Here, the authors report on cyclic peptides with low viscosity for catheter delivery, which form self-assembled peptide hydrogels following enzymatic cleavage and demonstrated delivery in vivo.

The positional effect of stimuli-responsive units in tri-component copolymer vesicles is studied to explore variations in the host–guest properties of the assembly. We study this by placing pH-responsive diisopropylaminoethyl moieties in three distinct locations of a block copolymer assembly. In two of the three variations, these functionalities were randomly distributed in the hydrophobic or the hydrophilic domains of an amphiphilic diblock copolymer. In a third variation, this responsive functionality was incorporated as the middle block in a triblock copolymer. The results reveal that the solvent exposure of the responsive units holds the key for controlling the rate of molecular release from these polymer vesicles. The study also shows that equilibrium changes in the morphology of an assembly are not good indicators of the responsive host–guest properties of a polymer assembly.

We report the one-pot aqueous phase synthesis of cisplatin drug loaded micellar nanoparticles using Ring-Opening Metathesis Polymerization-Induced Self-Assembly (ROMPISA). ROMPISA was used to generate a small library of nanoparticles to examine the effect of size and charge on their action as cytotoxic agents against human ovarian and cervical cancer cells in vitro. The results show that polymerization-induced self-assembly (PISA) can easily yield drug loaded nanoparticles in one step at high solids concentrations in water for formulation of drugs at cytotoxic levels.

We have considered three two-dimensional (2D) π-conjugated polymer network (i.e., covalent organic frameworks, COFs) materials based on pyrene, porphyrin, and zinc-porphyrin cores connected via diacetylenic linkers. Their electronic structures, investigated at the density functional theory global-hybrid level, are indicative of valence and conduction bands that have large widths, ranging between 1 and 2 eV. Using a molecular approach to derive the electronic couplings between adjacent core units and the electron-vibration couplings, the three π-conjugated 2D COFs are predicted to have ambipolar charge-transport characteristics with electron and hole mobilities in the range of 65–95 cm2 V−1 s−1. Such predicted values rank these 2D COFs among the highest-mobility organic semiconductors. In addition, we have synthesized the zinc-porphyrin based 2D COF and carried out structural characterization via powder X-ray diffraction, high-resolution transmission electron microscopy, and surface area analysis, which demonstrates the feasibility of these electroactive networks. Steady-state and flash-photolysis time-resolved microwave conductivity measurements on the zinc-porphyrin COF point to appreciable, broadband photoconductivity while transmission spectral measurements are indicative of extended π-conjugation.

In this paper, we show that gadolinium-loaded synthetic melanin nanoparticles (Gd(III)-SMNPs) exhibit up to a 40-fold enhanced photoacoustic signal intensity relative to synthetic melanin alone and higher than other metal-chelated SMNPs. This property makes these materials useful as dual labeling agents because Gd(III)-SMNPs also behave as magnetic resonance imaging (MRI) contrast agents. As a proof-of-concept, we used these nanoparticles to label human mesenchymal stem cells. Cellular uptake was confirmed with bright-field optical and transmission electron microscopy. The Gd(III)-SMNP-labeled stem cells continued to express the stem cell surface markers CD73, CD90, and CD105 and proliferate. The labeled stem cells were subsequently injected intramyocardially in mice, and the tissue was observed by photoacoustic and MR imaging. We found that the photoacoustic signal increased as the cell number increased (R(2) = 0.96), indicating that such an approach could be employed to discriminate between stem cell populations with a limit of detection of 2.3 × 10(4) cells in in vitro tests. This multimodal photoacoustic/MRI approach combines the excellent temporal resolution of photoacoustics with the anatomic resolution of MRI.

RNA interference (RNAi) requires the intracellular delivery of RNA molecules to initiate the neutralization of targeted mRNA molecules, inhibiting the expression or translation of the targeted gene. Current polymers and lipids that are used to deliver RNA molecules are generally required to be positively charged, to achieve complexation with RNA and the cellular internalization. However, positive surface charge has been implicated as the reason for toxicity in many of these systems. Herein, we report a novel strategy to generate noncationic RNA-polymer complexes for RNA delivery with low cytotoxicity. We use an in situ electrostatic complexation using a methylated pyridinium group, which is simultaneously removed during the RNA binding step. The resultant complexes demonstrate successful knockdown in preimplantation mammalian embryos, thus providing a new approach for nucleic acid delivery.