Microgel Core Research Articles

Catalyzed Henry Reaction by Compartmentalized Copper‐Pyrazolyl‐Complex Modified Microgels

AbstractCompartmentalization of homogeneous catalysts enhances their catalytic performance and can even increase the selectivity. Microgels can serve as smart catalyst carrier systems offering the compartmentalization combined with good accessibility of the catalyst enabling the recyclability and re‐usability. Yet, the incorporation of coordination complexes into microgels has not been studied systematically, lacking in detailed insight in their structure and catalytic performance. Herein, microgels are synthesized with controlled number and localization of copper(II)‐pyrazolyl‐complexes. The catalytic activity of microgels in the Henry reactions is examined showing significantly higher yields compared to pure copper(II)‐pyrazolyl‐complexes. Furthermore, the localization of the copper(II)‐pyrazolyl‐complexes in the microgel core resulted in higher product yields than for microgel catalysts with copper(II) complexes in the shell. Microgel catalysts are demonstrated with copper(II) complexes that can be used in numerous reaction cycles, allow re‐loading of copper to recover catalytically active centers, and can be applicable in industrially‐relevant catalytic processes.

A novel bioartificial pancreas fabricated via islets microencapsulation in anti-adhesive core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo.

Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to transplantation failure. Herein, a novel bioartificial pancreas is constructed via islets microencapsulation in core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Specifically, a hydrogel scaffold containing methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and vascular endothelial growth factor (VEGF) is fabricated, which can delivery VEGF in a sustained style and thus induce subcutaneous angiogenesis. In addition, islets-laden core-shell microgels using methacrylated hyaluronic acid (HAMA) as microgel core and poly(ethylene glycol) diacrylate (PEGDA)/carboxybetaine methacrylate (CBMA) as shell layer are prepared, which provide a favorable microenvironment for islets and simultaneously the inhibition of host immune rejection via anti-adhesion of proteins and immunocytes. As a result of the synergistic effect between anti-adhesive core-shell microgels and prevascularized hydrogel scaffold, the bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days. We believe this bioartificial pancreas and relevant fabrication method provide a new strategy to treat type 1 diabetes, and also has broad potential applications in other cell therapies.

Polymer Stabilized Metal Nanoparticles for Catalytic Degradation of Methylene Blue in Water

Methylene blue is highly toxic and releases from various industries. It must be transformed into less toxic compounds. The Core-Shell microgels p (Pst core), Pstcore-NIPMamm-MAa and Ag in Pst-p NIPMamm-MAa have been synthesized using the Core-Shell hybrid micro gelling NIPMamm-MAa emulsion polymerization process. The 0.086mM, MB 6.2mM NaBH4 and 0.2916 mg / mL catalysts in the cuvette were measured using UV-visible spectrophotometers. Spectrums were measured at a one-minute interval. The peak at 600 nm steadily decreased over time and was completely eliminated after 11 minutes. Without the catalyst, MB decreases with NaBH4 which showed that the reaction decreases were slow and MB very high within 120 minutes. The Psty core of FT-IR core microgels, pNIpmam-MMAA, and Ag-pNIpmam-MAA core microgels are hybrids. At 2955 and 2845 cm−1 FT-IR spectra, Psty NiPMaM – MaA and Ag-p NiPMaM – MaA were used for core shell microgels, with C-H vibrations expanding the aromatic ring. In this study degradation of Methylene were carried out with Ag- Nanocomposites at different interval of time to check the degradation at minimum time. The degradation of MB dye

Multifunctional Core-Shell Microgels as Pd-Nanoparticle Containing Nanoreactors With Enhanced Catalytic Turnover.

In this work, we present core-shell microgels with tailor-made architecture and properties for the incorporation of palladium nanoparticles. The microgel core consists of poly-N-isopropylacrylamide (PNIPAM) copolymerized with methacrylic acid (MAc) as anchor point for the incorporation of palladium nanoparticles. The microgel shell is prepared by copolymerization of NIPAM and the UV-sensitive comonomer 2-hydroxy-4-(methacryloyloxy)-benzophenone (HMABP). The obtained core-shell architecture was analyzed by means of photon correlation spectroscopy, while the incorporated amount of HMABP was further confirmed via Fourier transform infrared spectroscopy. Subsequently, the microgel system was used for loading with palladium nanoparticles and their size and localization were investigated by transmission electron microscopy. The catalytic activity of the monodisperse palladium nanoparticles was tested by reduction of 4-nitrophenol to 4-aminophenol. The obtained reaction rate constants for the core-shell system showed enhanced activity compared to the Pd-loaded bare core system. Furthermore, it was possible to recycle the catalyst several times. Analysis via transmission electron microscopy revealed, that the incorporated palladium nanoparticles emerged undamaged after the reaction and subsequent purification process since no aggregation or loss in size was observed.

Temperature-induced unloading of liposomes bound to microgels

Bilayer lipid vesicles (liposomes) composed of zwitter-ionic (electroneutral) egg yolk lecithin and anionic phosphatidylserine were loaded with a water-soluble antitumor antibiotic Dox and electrostatically adsorbed onto the surface of thermo-sensitive microgels synthesized from 3-( N,N -dimethylamino)propylmethacrylamide, N,N -methylenebisacrylamide and 2,2′-azobis(2-methylpropionamidine) dihydrochloride. The resulting saturated microgel-liposomes complex with ultimately adsorbed 40 liposomes retains encapsulated drug in water solution at 25 °C. An increase in temperature induces a collapse of the microgel core and squeezing of the liposome shell, followed by liposome disruption and a release of encapsulated Dox. An intensive Dox leakage begins when temperature reaches 39 °C; a maximum amount of Dox is released within 5 min after starting the temperature trigger. The results are of importance for constricting of thermo-sensitive drug carries and developing protocols for the most productive drug release. • Anionic liposomes preserve their integrity after binding to cationic microgels. • Thermo-induced collapse of microgel core destroys the outer liposome layer. • Liposome disruption is accompanied by a fast release of encapsulated drug. • Sharp rise in the released drug was observed in between 39 and 41 °C. • Rigid latex particles bound to microgels form incompressible outer shell.

Insight into multilayered alginate/chitosan microparticles for oral administration of large cranberry fruit extract

• Up to 7 layers (CHIT and ALG mv ) shell were built on the CFE-loaded ALG-based cores. • The shell was a non-lamellar, interpenetrating network of oppositely charged polysaccharides. • The mechanical resistance depends on the type of ALG used as the core material and the shell structure. • The three-layered microcapsules showed the best performance in the in vitro release study. • The applicability of the studied particles could be controlled by their core and shell structure. We present a series of multilayered alginate/chitosan microparticles fabricated via combining ionic gelation with the layer-by-layer (LbL) approach to improve oral administration of large cranberry fruit extract (CFE). Sodium alginate of low (ALG lv ) or medium (ALG mv ) viscosity was used as a core polymer, and chitosan (CHIT) and ALG mv layers were alternately assembled to form up to seven layers’ coating. Microparticles size ranged between 640 and 1120 μm, and their morphology, moisture content, and structural integrity were affected mainly by the outermost layer’s composition. Both the microgel core and shell composition of these microparticles influenced the mechanical properties determined by the parallel plates compression test. Microparticles exhibited good CFE entrapment efficiency (E.E. > 55%) and favorable release profiles in the simulated gastro-intestine environment, well described by the hybrid model of the release kinetics. Our results evidence that polysaccharide-inspired microparticles are good platforms for enhancing the oral bioavailability of poorly water-soluble therapeutic agents.

Raspberry structures in microgel–silica nanoparticle composite systems

Composite materials consisting of responsive microgels together with additional nanoparticles might provide new and “smart” functionality, e.g. uptake and release of nanoparticles, or special mechanical or rheological properties of a solution. Here, composites consisting of PNIPAM microgels and silica nanoparticles have been investigated by CryoTEM and neutron scattering techniques. The formation of “raspberry” like core–shell structures with a silica nanoparticle layer around the microgel core has been observed.

Colloidal and polymeric contributions to the yielding of dense microgel suspensions

HypothesisSoft microgel colloids can be densely packed since particle networks can compress and interpenetrate. This evolution of the particle’s internal structure associated with packing is expected to determine the linear viscoelastic properties and the yielding behavior of dense suspensions of microgel colloids. ExperimentsWe investigated the volume fraction-dependent linear and non-linear rheological response of suspensions of soft core-shell particles formed by a poly(N-isopropylacrylamide) (PNIPAM) microgel core and a thin poly(ethylene glycol) (PEG) shell. FindingsThe linear viscoelasticity of suspensions reveals a transition from a fluid to a jammed glass state. Increasing volume fraction within the jammed state, the linear storage modulus and the yield stress show distinct regimes associated with the evolution of particle contacts, which involve progressive compression and interpenetration of the shell and core. The yielding of jammed suspensions occurs in two-steps: At small strains jammed cages are rearranged, while full disentanglement of interpenetrating networks only occurs at large deformations and results in fluidization. Yield strains and stresses increase with increasing shear rate or frequency, suggesting a progressive dominance of the timescale associated with shear over that associated with the internal dynamics of the system.

Design and Synthesis of Core–Shell Microgels with One‐Step Clickable Crosslinked Cores and Ultralow Crosslinked Shells

AbstractThe present study is conducted to explore the engineering of core–shell microgels such that the core can be rapidly labeled with a variety of fluorophores, while the shell retains the softness needed in specific biomedical applications. Azide containing crosslinked core particles based on a crosslinked poly(N‐isopropylacrylamide) particle, using a one‐pot, multistep polymerization is synthesized. A core–shell microgel is then synthesized by growing a crosslinker‐free poly(N‐isopropylacrylamide)‐co‐acrylic acid (ULC10AAc) shell through a two‐step seed and feed polymerization. A simple “click” reaction between the azide present on the core and dibenzocyclooctyne containing fluorophores to make dyed core–shell microgels is further demonstrated. This approach toward dyed core–shell microgels eliminates the difficulty of crossreactivity between shell‐localized chemoligation sites and the core‐localized functionalities. The use of strained‐ring systems to achieve the click reaction eliminates the use of cytotoxic catalysts common in traditional click chemistry. This approach allows not only to label the microgel core with different fluorophores but also to synthesize multiprobe core–shell microgel by simultaneously labeling a microgel core with multiple different fluorophores.

Double security drug delivery system DDS constructed by multi-responsive (pH/redox/US) microgel

In this paper, the multi-responsive core-shell microgels were prepared for constructing a double-locked drug delivery system. The pH- sensitive poly(2-(diisopropylamino ethylmethacry-late)-block-poly(ethyleneimine) diblock copolymers (PDPA-b-PEI) were synthesized and used to prepare micelles through their self-assembly in neutral solution. Redox-responsive gel shells were formed by Michael addition of primary amine group of branched PEI using disulfide as a cross-linker, which was specifically cleaved by glutathione (GSH). Anticancer drug doxorubicin DOX and perfluorohexane (PFH) could be encapsulated in the core of microgel. The DOX was released sustainably only under the condition of pH and GSH were both right. For example, under neutral condition with GSH, DOX could not release swimmingly due to the core of microgels was in hydrophobic state and wrapped the DOX firmly, although the gel shells were collapsed by GSH. When exposed to ultrasound, the drug released abruptly and achieved a complete release instantly. Moreover, it was found that the structure of the microgels was not destroyed after the ultrasound stimulus but had undergone an expansion-recovery process. Finally, it was demonstrated that the microgel had a “double security” effect, ensuring the low drug leakage during the normal blood circulation and efficient drug release under the pH/redox/ultrasound stimulus. The multi-responsive microgels designed here, which combines the usage of both endogenous and exogenous stimuli, has the advantages of low side-effect, high spatiotemporal controllability and complete release.

Deswelling studies of pH and temperature-sensitive ultra-low cross-linked microgels with cross-linked cores

Microgels prepared without exogenous crosslinker have recently been explored for diverse applications in biotechnology. However, our fundamental understanding of structure-property relationships for this class of materials is still lacking, especially in the context of more complex structures such as core-shell particles. In this article, core-shell microgels were prepared by seed-mediated, surfactant-free emulsion polymerization using a N,N′-methylenebis (acrylamide) (BIS) cross-linked poly(N-isopropylacrylamide) (pNIPAm) microgel core upon which a crosslinker-free poly(N-isopropylacrylamide)-co-acrylic acid (ULC10AAc) shell was synthesized. Dynamic light scattering (DLS) and phase analysis light scattering (PALS) measurements show that the hydrodynamic radius and electrophoretic mobility of the core-shell microgels increase significantly with increasing pH due to the pH responsive ULC10AAc shell, while the temperature sensitivity of the microgels is also strongly pH dependent. The turbidity and the temperature-dependent scattering intensity plots of microgels at different pH also provide insight into the charged state of the microgels under the studied conditions. For example, we observe multiple temperature-induced transitions when the pH is either 4.5 or 6.5, illustrating that the core and shell domains, while remaining mechanically connected, are only partially coupled thermodynamically. These studies provide insight into the perturbation of ULC microgel behavior that might be brought about due to the presence of a higher density core region. Complex architectures such as these are relevant in biotechnology applications where the soft, deformable ULC shell is advantageous to control the polymer-biology interface, but a denser core region might be required to obtain a higher loading of encapsulated therapeutics, tracking dyes, or oligonucleotides. Thus, it is important to understand the synthetic conditions that allow a ULC shell to remain “ULC-like” despite the presence of a denser core.

Poly-N-isopropylacrylamide Nanogels and Microgels at Fluid Interfaces.

The confinement of colloidal particles at liquid interfaces offers many opportunities for materials design. Adsorption is driven by a reduction of the total free energy as the contact area between the two liquids is partially replaced by the particle. From an application point of view, particle-stabilized interfaces form emulsions and foams with superior stability. Liquid interfaces also effectively confine colloidal particles in two dimensions and therefore provide ideal model systems to fundamentally study particle interactions, dynamics, and self-assembly. With progress in the synthesis of nanomaterials, more and more complex and functional particles are available for such studies. In this Account, we focus on poly(N-isopropylacrylamide) nanogels and microgels. These are cross-linked polymeric particles that swell and soften by uptaking large amounts of water. The incorporated water can be partially expelled, causing a volume phase transition into a collapsed state when the temperature is increased above approximately 32 °C. Soft microgels adsorbed to liquid interfaces significantly deform under the influence of interfacial tension and assume cross sections exceeding their bulk dimensions. In particular, a pronounced corona forms around the microgel core, consisting of dangling chains at the microgel periphery. These polymer chains expand at the interface and strongly affect the interparticle interactions. The particle deformability therefore leads to a significantly more complex interfacial phase behavior that provides a rich playground to explore structure formation processes. We first discuss the characteristic "fried-egg" or core-corona morphology of individual microgels adsorbed to a liquid interface and comment on the dependence of this interfacial morphology on their physicochemical properties. We introduce different theoretical models to describe their interfacial morphology. In a second part, we introduce how ensembles of microgels interact and self-assemble at liquid interfaces. The core-corona morphology and the possibility to force these elements into overlap upon compression results in a complex phase behavior with a phase transition between microgels with extended and collapsed coronae. We discuss the influence of the internal particle architecture, also including core-shell microgels with rigid cores, on the phase behavior. Finally, we present new routes for the realization of more complex structures, resulting from multiple deposition protocols and from engineering the interaction potential of the individual particles.

Synthesis and characterization of poly(N-isopropylacrylamide-co-N,N′-methylenebisacrylamide-co-acrylamide) core – Silica shell nanoparticles by using reactive surfactant polyoxyethylene alkylphenyl ether ammonium sulfate

We report a novel approach based on using polyoxyethylene alkylphenyl ether ammonium sulfate (HS10) as an anion reactive surfactant, which greatly reduced the size of poly(N-isopropylacrylamide-co-acrylamide-co-N,N′-methylenebisacrylamide) [P(NIPAM/AM/MBA)] microgel core – silica shell particles. First, the microgel cores were synthesized by copolymerization of N-isopropylacrylamide (NIPAM), N,N′-methylenebisacrylamide (MBA) with a variation of acrylamide (AM) and HS10 concentration in water. It followed by silica encapsulation of the microgel cores via the addition of 3-glycidyloxypropyltrimethoxysilane (GLYMO) and tetraethyl orthosilicate (TEOS) at alkaline environment (pH 12). It is interesting to note that the size of both PNIPAM-based microgel cores and PNIPAM-based microgel core – silica shell particles were well-controlled by using a small level of HS10. Furthermore, SEM images of the hybrid core – shell particles show the well-defined spherical morphology with monodisperse particle size distribution. As expected, HS10-containing samples are covered by the porous silica shell layer, instead of continuous silica shell obtained from HS10-free samples observed in TEM images. This novel incorporation not only well controls the core size and shell morphology, leading to increase their specific surface area but also does not greatly affect the thermo-sensitivity of final products. The resultant thermo-responsive microgel core – silica shell particles with controlled particle morphology and physicochemical properties are useful for biomedical application fields.

Improved Smart Microgel Carriers for Catalytic Silver Nanoparticles.

Acrylamide-based, thermoresponsive core–shell microgels with a linear phase transition region are used as improved carriers for catalytically active silver nanoparticles in the present study. In this context, we investigated the swelling behavior of the carriers and the stability of the silver nanoparticles inside the polymer network with photon correlation spectroscopy, transmission electron microscopy, and by following the surface plasmon resonance of the nanoparticles. Depending on the cross-linker content of the microgel core, we observed very good stability of the nanoparticles inside the microgel network, with nearly no bleeding or aggregation of the nanoparticles over several weeks for core cross-linker contents of 5 and 10 mol %. The architecture of the hybrid particles in the swollen state was investigated with cryogenic transmission electron microscopy. The particles exhibit a core–shell structure, with the silver nanoparticles located mainly at the interface between the core and shell. This architecture was not used before and seems to grant advanced stability to the nanoparticles inside the network in combination with good switchability of the catalytic activity. This was measured by following the reduction of 4-nitrophenole, which is a well-studied model reaction. The obtained Arrhenius plots show that similar to previous works, the swelling of the core and shell can influence the catalytic activity of the silver nanoparticles. As mentioned before, the cross-linker content of the core seems to be a very important parameter for the switchability of the catalytic activity. A higher cross-linker content of the core seems to be connected to a stronger influence of the carrier swelling degree on the catalytic activity of the silver nanoparticles.

Synthesis and characterization of PNIPAM microgel core–silica shell particles

We developed a simple effective approach to prepare poly(N-isopropylacrylamide-co-acrylamide-co-N,N′-methylenebisacrylamide) (PNIPAM/AM/MBA) microgel core–silica shell particles with narrow particle size distribution via the sol–gel reaction of silica precursor deposited directly on the microgel particle surface in the presence of 3-glycidyloxypropyltrimethoxysilane (GLYMO). MBA was used as the cross-linking agent for the formation of microgel with the cross-linked network structure and GLYMO used as a coupling agent. The morphology of hybrid core–shell particles including the shape, core size, shell thickness and surface roughness was governed by the key components of AM and GLYMO. PNIPAM/AM/MBA microgel core–silica shell particles show desirable spherical shape, distinct core–shell structure and raspberry-like particle morphology. In contrast, PNIPAM/MBA microgel core–silica shell particles formed without resort to AM and GLYMO result in very poor silica encapsulation, thereby leading to undesired particle morphology. Incorporation of AM units into PNIPAM/MBA microgel particles increases the lower critical solution temperature (LCST). Furthermore, encapsulation of PNIPAM/AM/MBA microgel particles by silica does not affect the LCST to an appreciable extent, but it greatly reduces the thermo-sensitivity of the hybrid core–shell particles. Finally, the feasibility of using these PNIPAM-based core–silica shell particles as drug carriers was demonstrated.

Distribution of CoFe2O4 Nanoparticles Inside PNIPAM-Based Microgels of Different Cross-linker Distributions.

The aim of this study is to tailor the inner structure of positively charged poly-( N-isopropylacrylamid- co-allylamine) (P(NIPAM- co-AA)) microgels for a better control of the distribution of negatively charged magnetic cobaltferrite (CoFe2O4@CA) nanoparticles (MNPs) within the microgels. Therefore, two different strategies are followed for the microgel synthesis: the (one pot) batch method which leads to a higher cross-linker density in the microgel core and the feeding method which compensates different reaction kinetics of the cross-linker and the monomers. The latter one is expected to result in a homogeneous cross-linker distribution. Information about the cross-linker distribution is indirectly gained by measuring the elastic modulus via indentation experiments with an atomic force microscope. While the batch method results in a higher elastic modulus in the center of the microgel indicating a core/shell structure, the feeding method leads to a constant elastic modulus over the whole microgel. The loading with MNPs and their distribution are studied with transmission electron microscopy (TEM). The TEM images show a large difference in the MNP distribution which is correlated to the cross-linker distribution of both types of microgels. The batch method microgel has a low MNP concentration in the core. The feeding method microgel shows a much more homogeneous distribution of MNPs across the microgel. The latter one also shows a stronger charge reversal which is a hint for a higher loading of the feeding method microgel. Dynamic light scattering and electrophoretic mobility measurements demonstrate that for both types of microgels, the temperature sensitivity is preserved after loading with MNPs.

Fabrication of curcumin-loaded whey protein microgels: Structural properties, antioxidant activity, and in vitro release behavior

This study evaluated the potential use of whey protein microgels (WPM) formed by heating a protein solution at pH 5.90 as carriers for curcumin. The results indicated that the loading amount of curcumin into whey protein isolate (WPI) and WPM was 1.84 ± 0.18 and 17.51 ± 0.46 μg curcumin/mg protein, respectively. Loading of microgels with curcumin significantly increased their diameter and changed their surface charge. Loading of curcumin in the whey protein microgels drastically decreased its sedimentation during storage. Fluorescence measurements revealed that the curcumin was present at the hydrophobic core of whey protein microgels. X-ray diffraction analysis also showed that curcumin was loaded inside the WPM in an amorphous form. Curcumin-loaded whey protein microgels showed a high in vitro antioxidant activity which was measured by DPPH radical scavenging and reducing power assay. The in vitro release experiment also showed that the release of curcumin from WPM was significantly slower than WPI during the simulated gastrointestinal conditions. These findings suggested a possible utilization of WPI microgels in improving the applications of curcumin for the production of functional food products and drugs.

Microgels as carriers of antimicrobial peptides – Effects of peptide PEGylation

Delivery systems are likely to be central for the translation of antimicrobial peptides (AMPs) towards therapeutics. Addressing AMP interactions with microgel carriers, we here investigate how poly(ethylene glycol) conjugation (‘PEGylation’) of AMPs affect their loading and release to/from microgels, combining structural studies using nuclear magnetic resonance (NMR) with ellipsometry, circular dichroism spectroscopy (CD), and light scattering. Such studies demonstrate that poly(ethyl acrylate-co-methacrylic acid) microgels bind considerable amounts of the positively charged AMP KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR) and its PEGylated variants KYE28-PEG48, PEG48-KYE28, and PEG24-KYE28-PEG24. Z-potential measurements indicate that KYE28 resides primarily inside the microgel core, and that localization of the PEGylated peptides is shifted towards the microgel corona. Furthermore, while all peptides are disordered in solution, CD measurements report on helix induction on microgel binding, particularly so for the PEGylated peptides. Addressing such conformational changes in more detail, NMR structural studies showed that peptide-microgel interactions are facilitated by a hydrophobic domain formed by the peptide after microgel binding, and with modulating electrostatic/salt bridge interaction between the positively charged peptide residues and negative microgel charges. As the microgels remain negatively charged also at high peptide load, membrane disruption and antimicrobial effects necessitates peptide release, demonstrated to be promoted by PEGylation and high ionic strength. Importantly, microgel loading, as well as peptide localization, conformation, and release, did not depend significantly on PEG conjugation site, but instead seems to be dictated by the PEG content of the peptide conjugates.

Brush-First and ROMP-Out with Functional (Macro)monomers: Method Development, Structural Investigations, and Applications of an Expanded Brush-Arm Star Polymer Platform.

The efficient synthesis of complex functional polymeric nanomaterials is often challenging. Ru-initiated ring-opening metathesis polymerization (ROMP) of multivalent macromonomers followed by cross-linking to form brush-arm star (BASP) polymers enables access to well-defined nano-structures with diverse functionality. This "brush-first" method leaves active Ru in the BASP microgel core, which could potentially be used in a subsequent "ROMP-out" (RO) step to introduce further modifications to the BASP structure via the addition of (macro)monomers. Here, we study this RO approach in depth. The efficiency of RO is assessed for a variety of BASP compositions using a combination of inductively coupled plasma mass spectrometry and gel permeation chromatography. To demonstrate the modularity of the RO process, arylboronic acid-functionalized BASPs were prepared; uptake of these RO-BASPs into hypersialylated cancer cells was enhanced relative to non-functionalized BASPs as determined by flow cytometry and fluorescence microscopy. In addition, the self-assembly of miktoarm BASPs prepared via brush-first and RO with different macromonomers is demonstrated. The combination of brush-first ROMP with RO provides a simple, modular strategy for access to a wide array of functional nanomaterials.

Conformational Aspects of High Content Packing of Antimicrobial Peptides in Polymer Microgels.

Successful use of microgels as delivery systems of antimicrobial peptides (AMPs) requires control of factors determining peptide loading and release to/from the microgels as well as of membrane interactions of both microgel particles and released peptides. Addressing these, we here investigate effects of microgel charge density and conformationally induced peptide amphiphilicity on AMP loading and release using detailed nuclear magnetic resonance (NMR) structural studies combined with ellipsometry, isothermal titration calorimetry, circular dichroism, and light scattering. In parallel, consequences of peptide loading and release for membrane interactions and antimicrobial effects were investigated. In doing so, poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate the cationic AMPs EFK17a (EFKRIVQRIKDFLRNLV) and its partially d-amino acid-substituted variant EFK17da (E(dF)KR(dI)VQR(dI)KD(dF)LRNLV). Peptide incorporation was found to increase with increasing with microgel charge density and peptide amphiphilicity. After microgel incorporation, which appeared to occur preferentially in the microgel core, NMR showed EFK17a to form a helix with pronounced amphiphilicity, while EFK17da displayed a folded conformation, stabilized by a hydrophobic hub consisting of aromatic/aromatic and aliphatic/aromatic interactions, resulting in much lower amphiphilicity. Under wide ranges of peptide loading, the microgels displayed net negative z-potential. Such negatively charged microgels do not bind to, nor lyse, bacteria-mimicking membranes. Instead, membrane disruption in these systems is mediated largely by peptide release, which in turn is promoted at higher ionic strength and lower peptide amphiphilicity. Analogously, antimicrobial effects against Escherichia coli were found to be dictated by peptide release. Taken together, the findings show that peptide loading, packing, and release strongly affect the performance of microgels as AMP delivery systems, effects that can be tuned by (conformationally induced) peptide amphiphilicity and by microgel charge density.