12 research outputs found
Relating Side Chain Organization of PNIPAm with its Conformation in Aqueous Methanol
Combining nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and ÎŒs 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, methanolâPNIPAm 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 surfactantîžsodium
dodecyl sulfate or Lutensol AT50, respectivelyîžwas 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 polyÂ(vinylferrocene)-<i>block</i>-polyÂ(ethylene glycol) (PVFc-<i>b</i>-PEG)
diblock copolymers (<i>M</i><sub>n</sub> = 13âŻ000â44âŻ000
g mol<sup>â1</sup>; <i>Ä</i> = 1.29â1.34)
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)â<i>b</i>âpoly(lactide) Diblock and Miktoarm Star Polymers and Their Behavior in Solution
The synthesis of diblock and miktoarm
star polymers containing
polyÂ(vinylferrocene) (PVFc) and polyÂ(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 AB<sub>2</sub> miktoarm star polymers
was synthesized with varied PLA chain lengths. All polymers were characterized
in detail, using <sup>1</sup>H 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 AB<sub>2</sub> miktoarm star polymers are in the range of 8000â15000,
containing a PVFc block of weight 7800. In addition, the self-assembly
behavior of the polymers in dichloromethane (CH<sub>2</sub>Cl<sub>2</sub>) 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