Carbohydrate-Based Nanocarriers Exhibiting Specific Cell Targeting with Minimum Influence from the Protein Corona.

Whenever nanoparticles encounter biological fluids like blood, proteins adsorb on their surface and form a so-called protein corona. Although its importance is widely accepted, information on the influence of surface functionalization of nanocarriers on the protein corona is still sparse, especially concerning how the functionalization of PEGylated nanocarriers with targeting agents will affect protein corona formation and how the protein corona may in turn influence the targeting effect. Herein, hydroxyethyl starch nanocarriers (HES-NCs) were prepared, PEGylated, and modified on the outer PEG layer with mannose to target dendritic cells (DCs). Their interaction with human plasma was then s…

Kohlenhydrat-basierte Nanocarrier mit spezifischem Zell-Targeting und minimalem Einfluss durch die Proteinkorona

Sobald Nanopartikel mit biologischen Flussigkeiten wie Blut in Kontakt kommen, adsorbieren Proteine auf ihrer Oberflache, welche die sogenannte Proteinkorona ausbilden. Die Wichtigkeit dieser Proteinhulle ist weitgehend anerkannt, jedoch untersuchen nur wenige Studien den Einfluss von Oberflachenfunktionalisierung der Nanocarrier auf die Proteinkorona. Vor allem die Variation der Proteinkorona von PEGylierten und zusatzlich mit Targeting-Molekulen versehenen Nanotragern und der Einfluss auf das Targeting sind nicht bekannt. Hydroxyethylstarke-Nanocarrier (HES-NCs) wurden synthetisiert, anschliesend PEGyliert und zusatzlich (“on top”) mit Mannose funktionalisiert, um dendritische Zellen (DCs…

Redox-Responsive Block Copolymers: Poly(vinylferrocene)-b-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 detai…

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

The synthesis of high-molecular-weight, well-defined poly(vinylferrocene)-block-poly(ethylene glycol) (PVFc-b-PEG) diblock copolymers (Mn = 13 000–44 000 g mol–1; Đ = 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-b-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 cyclo…

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 (EC50 ) for loaded TNF-α is reduced by more than two…

Drug Delivery: Dendritic Mesoporous Silica Nanoparticles for pH-Stimuli-Responsive Drug Delivery of TNF-Alpha (Adv. Healthcare Mater. 13/2017)

Heparin-Based Nanocapsules as Potential Drug Delivery Systems

Herein, the synthesis and characterization of heparin-based nanocapsules (NCs) as potential drug delivery systems is described. For the synthesis of the heparin-based NCs, the versatile method of miniemulsion polymerization at the droplets interface was achieved resulting in narrowly distributed NCs with 180 nm in diameter. Scanning and transmission electron microscopy images showed clearly NC morphology. A highly negative charge density for the heparin-based NCs was determined by measuring the electro-kinetic potential. Measuring the activated clotting time demonstrated the biological intactness of the polymeric shell. The ability of heparin-based NCs to bind to antithrombin (AT III) was i…