Relating Side Chain Organization of PNIPAm with its Conformation in Aqueous Methanol

Combining nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and μs long all-atom simulations with two million particles, we establish a delicate correlation between increased side chain organization of PNIPAm and its collapse in aqueous methanol mixtures. We find that the preferential binding of methanol with PNIPAm side chains, bridging distal monomers along the polymer backbone, results in increased organization. Furthermore, methanol–PNIPAm preferential binding is dominated by hydrogen bonding. Our findings reveal that the collapse of PNIPAm is dominated by enthalpic interactions and that the standard poor solvent (entropic) effects play no major role

Influence of different factors on the interaction between polymeric nanomaterials and blood plasma proteins

In recent years, nanomaterials received increasing attention for their application as drug delivery devices. Since most carriers are applied intravenously, a new biological interface is created after they interact with blood components: the protein corona. Proteins from the blood plasma adsorb to the nanocarrier surfaces and thereby change its characteristics. The adsorption process itself depends on many factors of which four different ones have been examined in this work. First, the effect of shear force during sample preparation of nanoparticle-protein complexes was examined and different analysis techniques were applied to compare the results. Second, the role of surfactants stabilizing the nanocarriers was investigated. In this context, first tests to develop a method for surfactant quantification in the presence of nanoparticles were successfully conducted. The third factor considered was the modification of proteins with fluorescent dyes, which is often used for biochemical techniques. At last, the protein adsorption was studied at different temperatures. It could be demonstrated that the comparison of the thermodynamic adsorption parameters can be used to determine the reversibility of the adsorption process. In summary, the detailed investigation of the different factors helps to understand the involved processes of protein adsorption and provides useful tools for future investigations

Small Surfactant Concentration Differences Influence Adsorption of Human Serum Albumin on Polystyrene Nanoparticles

Surfactants, even in miniscule amounts, are often used for the synthesis and especially the stabilization of nanomaterials, which is essential for in vivo applications. In this study, we show that the interaction between nanoparticles and proteins strongly depends on the type of stabilizing surfactants and their (small) concentration changes. The reaction between human serum albumin and polystyrene nanoparticles stabilized by an ionic or nonionic surfactantsodium dodecyl sulfate or Lutensol AT50, respectivelywas monitored using isothermal titration calorimetry. It was found that the amount of surfactant molecules on the surface significantly determines the protein binding affinity and adsorption stoichiometry, which is important for all nanomaterials coming into contact with biological components such as blood plasma proteins. Thus after synthesizing nanomaterials for in vivo applications as drug delivery agents, it is crucial to perform a detailed analysis of the obtained surface chemistry that accounts for the presence of minimal amounts of stabilizing agents

Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers

The current gold standard to reduce non-specific cellular uptake of drug delivery vehicles is by covalent attachment of poly(ethylene glycol) (PEG). It is thought that PEG can reduce protein adsorption and thereby confer a stealth effect. Here, we show that polystyrene nanocarriers that have been modified with PEG or poly(ethyl ethylene phosphate) (PEEP) and exposed to plasma proteins exhibit a low cellular uptake, whereas those not exposed to plasma proteins show high non-specific uptake. Mass spectrometric analysis revealed that exposed nanocarriers formed a protein corona that contains an abundance of clusterin proteins (also known as apolipoprotein J). When the polymer-modified nanocarriers were incubated with clusterin, non-specific cellular uptake could be reduced. Our results show that in addition to reducing protein adsorption, PEG, and now PEEPs, can affect the composition of the protein corona that forms around nanocarriers, and the presence of distinct proteins is necessary to prevent non-specific cellular uptake

Alternative Pathway for the Stabilization of Reactive Emulsions via Cross-Linkable Surfactants

Highly reactive emulsions were stabilized by employing a surfmer analogous concept. An interfacial reaction between an emulsion droplet and a cross-linkable reactive surfactant was used to provide colloidal stability and simultaneously maintain the majority of the reactive groups. Polyaddition-type reaction between epoxy and amine was chosen as a model system to spontaneously and covalently bond the surfactant to the emulsion droplets. The interfacial reaction was monitored via isothermal titration calorimetry analysis. With this method, the increased colloidal stability could be attributed to a reaction rather than a pure physical adsorption. The maintained reactivity of the emulsion droplets enables consecutive conversions with coreactive components, e.g., for cross-linking reactions, corrosion protection, or functional coatings

Polyvinylferrocene-Based Amphiphilic Block Copolymers Featuring Functional Junction Points for Cross-Linked Micelles

The synthesis of high-molecular-weight, well-defined poly­(vinylferrocene)-<i>block</i>-poly­(ethylene glycol) (PVFc-<i>b</i>-PEG) diblock copolymers (<i>M</i>_n = 13 000–44 000 g mol^–1; <i>Đ</i> = 1.29–1.34) with precisely one allyl group at the junction point is introduced. Allyl glycidyl ether (AGE) was used to end-functionalize PVFc, resulting in hydroxyl functional macroinitiators for the oxyanionic polymerization of ethylene oxide. The self-assembly behavior of the amphiphilic PVFc-<i>b</i>-PEG copolymers in water has been investigated in a detailed manner, using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The redox activity of the PVFc block was confirmed by UV/vis spectroscopy, while cyclovoltammetry (CV) measurements were carried out to support the stability and full reversibility of the ferrocene/ferrocenium redox couple. Both formation and dissociation of the macromolecular self-assemblies in aqueous solution via oxidation and reduction of the PVFc segments were evidenced by TEM and DLS. The dye Nile Red was used as model compound to investigate the stabilization of a water-insoluble molecule in aqueous solution by the block copolymers via encapsulation inside micellar structures. Oxidation of the PVFc segments lead to instantaneous and quantitative release of the dye. Furthermore, incorporation of the allyl moiety at the block junction point was used to cross-link the shell of the compartments. By this strategy a stable incorporation of the dye was achieved while triggered release via oxidation led to quantitative liberation

Redox-Responsive Block Copolymers: Poly(vinylferrocene)‑<i>b</i>‑poly(lactide) Diblock and Miktoarm Star Polymers and Their Behavior in Solution

The synthesis of diblock and miktoarm star polymers containing poly­(vinylferrocene) (PVFc) and poly­(l-lactide) (PLA) blocks is introduced. End functionalization of PVFc was carried out via end capping of living carbanionic PVFc chains with benzyl glycidyl ether (BGE). By hydrogenolysis of the benzyl protecting group a dihydroxyl end-functionalized PVFc was obtained. Both monohydroxyl- and dihydroxyl-functionalized PVFcs have been utilized as macroinitiators for the subsequent polymerization of l-lactide via catalytic ring-opening polymerization. A series of block copolymers and AB₂ miktoarm star polymers was synthesized with varied PLA chain lengths. All polymers were characterized in detail, using ¹H NMR spectroscopy, size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF). The molecular weight of the block copolymers and AB₂ miktoarm star polymers are in the range of 8000–15000, containing a PVFc block of weight 7800. In addition, the self-assembly behavior of the polymers in dichloromethane (CH₂Cl₂) was investigated by using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In a selective solvent for PLA the block copolymers and miktoarm star polymers formed vesicle-like structures with different diameters

Dendritic mesoporous silica nanoparticles for pH-stimuli-responsive drug delivery of TNF-alpha

Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune stimulatory cytokine and natural endotoxin that can induce necrosis and regression in solid tumors. However, systemic administration of TNF-α is not feasible due to its short half-life and acute toxicity, preventing its widespread use in cancer treatment. Dendritic mesoporous silica nanoparticles (DMSN) are used coated with a pH-responsive block copolymer gate system combining charged hyperbranched polyethylenimine and nonionic hydrophilic polyethylenglycol to encapsulate TNF-α and deliver it into various cancer cell lines and dendritic cells. Half-maximal effective concentration (EC) for loaded TNF-α is reduced by more than two orders of magnitude. Particle stability and premature cargo release are assessed with enzyme-linked immunosorbent assay. TNF-α-loaded particles are stable for up to 5 d in medium. Tumor cells are grown in vitro as 3D fluorescent ubiquitination-based cell cycle indicator spheroids that mimic in vivo tumor architecture and microenvironment, allowing real-time cell cycle imaging. DMSN penetrate these spheroids, release TNF-α from its pores, preferentially affect cells in S/G2/M phase, and induce cell death in a time- and dose-dependent manner. In conclusion, DMSN encapsulation is demonstrated, which is a promising approach to enhance delivery and efficacy of antitumor drugs, while minimizing adverse side effects