Synergistic Anticancer Therapy by Ovalbumin Encapsulation-Enabled Tandem Reactive Oxygen Species Generation

2020

Abstract The anticancer efficacy of photodynamic therapy (PDT) is limited due to the hypoxic features of solid tumors. We report synergistic PDT/chemotherapy with integrated tandem Fenton reactions mediated by ovalbumin encapsulation for improved in vivo anticancer therapy via an enhanced reactive oxygen species (ROS) generation mechanism. O2 .− produced by the PDT is converted to H2O2 by superoxide dismutase, followed by the transformation of H2O2 to the highly toxic .OH via Fenton reactions by Fe2+ originating from the dissolution of co‐loaded Fe3O4 nanoparticles. The PDT process further facilitates the endosomal/lysosomal escape of the active agents and enhances their intracellular deliv…

Highly Loaded Semipermeable Nanocapsules for Magnetic Resonance Imaging.

2017

Magnetic resonance imaging has become an essential tool in medicine for the investigation of physiological processes. The key issues related to contrast agents, i.e., substances that are injected in the body for imaging, are the efficient enhancement of contrast, their low toxicity, and their defined biodistribution. Polyurea nanocapsules containing the gadolinium complex Gadobutrol as a contrast agent in high local concentration and high relaxivity up to 40 s-1 mmol-1 L are described. A high concentration of the contrast agent inside the nanocapsules can be ensured by increasing the crystallinity in the shell of the nanocapsules. Nanocapsules from aliphatic polyurea are found to display hi…

Temperature‐Responsive Nanoparticles Enable Specific Binding of Apolipoproteins from Human Plasma

2021

Apolipoproteins are an important class of proteins because they provide a so-called stealth effect to nanoparticles. The stealth effect on nanocarriers leads to a reduced unspecific uptake into immune cells and thereby to a prolonged blood circulation time. Herein, a novel strategy to bind apolipoproteins specifically on nanoparticles by adjusting the temperature during their incubation in human plasma is presented. This specific binding, in turn, allows a control of the stealth behavior of the nanoparticles. Nanoparticles with a well-defined poly(N-isopropylacrylamide) shell are prepared, displaying a reversible change of hydrophobicity at a temperature around 32 °C. It is shown by label-f…

Encapsulation of polyprodrugs enables an efficient and controlled release of dexamethasone

2021

Water-soluble low molecular weight drugs, such as the synthetic glucocorticoid dexamethasone (DXM), can easily leak out of nanocarriers after encapsulation due to their hydrophilic nature and small size. This can lead to a reduced therapeutic efficacy and therefore to unwanted adverse effects on healthy tissue. Targeting DXM to inflammatory cells of the liver like Kupffer cells or macrophages is a promising approach to minimize typical side effects. Therefore, a controlled transport to the cells of interest and selective on-site release is crucial. Aim of this study was the development of a DXM-phosphate-based polyprodrug and the encapsulation in silica nanocontainers (SiO2 NCs) for the red…

Versatile preparation of silica nanocapsules for biomedical applications

2020

Core–shell nanocapsules are receiving increasing interest for drug delivery applications. Silica nanocapsules have been the focus of intensive studies due to their biocompatibility, versatile silica chemistry, and tunable porosity. However, a versatile one-step preparation of silica nanocapsules with well-defined core–shell structure, tunable size, flexible interior loading, and tailored shell composition, permeability, and surface functionalization for site-specific drug release and therapeutic tracking remains a challenge. Herein, an interfacially confined sol–gel process in miniemulsion for the one-step versatile preparation of functional silica nanocapsules is developed. Uniform nanocap…

Fluorescence Correlation Spectroscopy in Dilute Polymer Solutions: Effects of Molar Mass Dispersity and the Type of Fluorescent Labeling

2015

Fluorescence correlation spectroscopy (FCS) has become an important tool in polymer science. Among various other applications the method is often applied to measure the hydrodynamic radius and the degree of fluorescent labeling of polymers in dilute solutions. Here we show that such measurements can be strongly affected by the molar mass dispersity of the studied polymers and the way of labeling. As model systems we used polystyrene and poly(methyl methacrylate) synthesized by atom transfer radical polymerization or free-radical polymerization. Thus, the polymers were either end-labeled bearing one fluorophore per chain or side-labeled with a number of fluorophores per chain proportional to…

Brush Conformation of Polyethylene Glycol Determines the Stealth Effect of Nanocarriers in the Low Protein Adsorption Regime

2021

For nanocarriers with low protein affinity, we show that the interaction of nanocarriers with cells is mainly affected by the density, the molecular weight, and the conformation of polyethylene glycol (PEG) chains bound to the nanocarrier surface. We achieve a reduction of nonspecific uptake of ovalbumin nanocarriers by dendritic cells using densely packed PEG chains with a "brush" conformation instead of the collapsed "mushroom" conformation. We also control to a minor extent the dysopsonin adsorption by tailoring the conformation of attached PEG on the nanocarriers. The brush conformation of PEG leads to a stealth behavior of the nanocarriers with inhibited uptake by phagocytic cells, whi…

Chemical Routes Toward Multicompartment Colloids

2012

The search for mimicking natural living and non-living systems with synthetic products leads to the fabrication of advanced colloidal morphologies with hierarchical micro- and nanostructures. Different chemical routes toward the synthesis of colloids with complex morphologies are presented and a tentative analogy between these routes and the four basic arithmetic operations is proposed.

Modulating Protein Corona and Materials–Cell Interactions with Temperature‐Responsive Materials

2021

Nanofibrous photocatalysts from electrospun nanocapsules

2017

We present the design of multicompartment metal oxide/silica nanofibrous photocatalysts by colloid-electrospinning and subsequent calcination. During the calcination process, silica nanomaterials are cemented to form the fibrous framework and metal oxide precursors are crystallized inside and onto the fibers. This multicompartment nanofibrous structure, constructed with nanoparticles and core-shell nanocapsules, is therefore beneficial for the separation of the materials and the light utilization due to the multiple reflections and scattering of incident light in the cavities. The photocatalytic activity of the fibers was verified by the successful degradation of a model dye rhodamine B. Th…

Multifunctional clickable and protein-repellent magnetic silica nanoparticles

2016

Silica nanoparticles are versatile materials whose physicochemical surface properties can be precisely adjusted. Because it is possible to combine several functionalities in a single carrier, silica-based materials are excellent candidates for biomedical applications. However, the functionality of the nanoparticles can get lost upon exposure to biological media due to uncontrolled biomolecule adsorption. Therefore, it is important to develop strategies that reduce non-specific protein-particle interactions without losing the introduced surface functionality. Herein, organosilane chemistry is employed to produce magnetic silica nanoparticles bearing differing amounts of amino and alkene func…

Controlling protein interactions in blood for effective liver immunosuppressive therapy by silica nanocapsules

2020

Immunosuppression with glucocorticoids is a common treatment for autoimmune liver diseases and after liver transplant, which is however associated with severe side-effects. Targeted delivery of glucocorticoids to inflammatory cells, e.g. liver macrophages and Kupffer cells, is a promising approach for minimizing side effects. Herein, we prepare core–shell silica nanocapsules (SiO2 NCs) via a sol–gel process confined in nanodroplets for targeted delivery of dexamethasone (DXM) for liver immunosuppressive therapy. DXM with concentrations up to 100 mg mL−1 in olive oil are encapsulated while encapsulation efficiency remains over 95% after 15 days. Internalization of NCs by non-parenchymal muri…

From In Silico to Experimental Validation: Tailoring Peptide Substrates for a Serine Protease.

2020

Smart nanocarriers for the transport of drugs to tumor cells are nowadays of great interest for treating cancer. The use of enzymatic stimuli to cleave peptide-based drug nanocapsules for the selective release of nanocapsule cargo in close proximity to tumor cells opens new possibilities in cancer research. In the present work, we demonstrate a methodology for finding and optimizing cleavable substrate sequences by the type II transmembrane serine protease hepsin, which is highly overexpressed in prostate cancer. The design and screening of combinatorial libraries in silico against the binding cavity of hepsin allow the identification of a panel of promising substrates with high-calculated …