Supramolecular hydrophobic guest transport system based on pillar[5]arene

A pillar[5]arene-based bioactive guest loading system has been developed, which can increase the solubility of the drug norharmane in aqueous medium, and also enable its pH-stimulated release. Furthermore, this supramolecular transport system reduces the toxicity of loaded gues

Graphene-Based Bacterial Filtration via Electrostatic Adsorption

Flexible graphene oxide (GO) microsheets with attached positively charged polymers, termed GOX microsheets, are efficient at bacterial adsorption, as they bind electrostatically to bacterial membranes’ negative surface charge. The authors explore an antimicrobial water filter application for GOX's extremely high surface area and its previously described efficient bacterial adsorption.Cellulose-fiber carrier material is functionalized with GOX microsheets to create an adsorption-based bacteria filtration material. The morphology and charge density (7.8 × 1019 g–1) of the prepared GOX fibers are determined by scanning electron microscopy and dye adsorption assay, and widefield fluorescence microscopy is used to visualize the adsorption of stained Escherichia coli bacterial cells on the fibers. GOX fibers are tested in filtration setups to investigate their bacteria removal performance. The experimental results, with 100 mg of GOX fibers filtering 2.4 × 109 colony-forming units (CFU) from an E. coli bacterial culture with 99.5% bacterial reduction, demonstrate the fibers’ high bacteria loading capacity. The electrostatic adsorption-based filtration mechanism allows the filter to be operated at higher flow rates than micropore membrane filters, while maintaining 3-log bacterial reduction. GOX filter materials removing bacteria via adsorption are a high flow rate alternative to current water filtration processes that rely on size-exclusion

Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli

Here, we demonstrate the synthesis of linear polyglycerols bearing multiple copies of mono and dimannosides [LPG40Man0.60 and LPG40(Manα1,2Man)0.60]. A method based on label-free microscale thermophoresis (MST) has been optimized to determine the direct binding affinity of multivalent mannosides for Escherichia coli (E. coli) strain ORN178 that produces the fimbriae protein FimH. We observed that the LPG40(Manα1,2Man)0.60 exhibited only a modest one-fold improvement in binding as compared to LPG40Man0.60. Nevertheless, both the multivalent mannosides displayed remarkably very low nM binding constant (Kd) in contrast to the high μM Kd of the single α-D-methylmannoside for intact E. coli ORN 178 particles. Furthermore, in an Adhesion-Inhibition Assay, both multivalent mannosides showed 50% inhibition of bacteria adhesion to the HT-29 colon cells at low μM concentrations

Chemoenzymatic Synthesis of D-Glucitol-Based Non-Ionic Amphiphilic Architectures as Nanocarriers

Newer non-ionic amphiphiles have been synthesized using biocompatible materials and by following a greener approach i.e., D-glucitol has been used as a template, and hydrophobic and hydrophilic segments were incorporated on it by using click chemistry. The hydrophilic segments in turn were prepared from glycerol using an immobilized Candida antarctica lipase (Novozym-435)-mediated chemoenzymatic approach. Surface tension measurements and dynamic light scattering studies reflect the self-assembling behavior of the synthesized amphiphilic architectures in the aqueous medium. The results from UV-Vis and fluorescence spectroscopy establish the encapsulation of guests in the hydrophobic core of self-assembled amphiphilic architectures. The results of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicate that the amphiphiles are well tolerated by the used A549 cell lines at all tested concentrations

Tunable Polyglycerol-Based Redox-Responsive Nanogels for Efficient Cytochrome C Delivery

The sensitivity of therapeutic proteins is a challenge for their use in biomedical applications, as they are prone to degradation and opsonization, thus limiting their potential. This demands for the development of drug delivery systems shielding proteins and releasing them at the site of action. Here, we describe the synthesis of novel polyglycerol-based redox-responsive nanogels and report on their potential as nanocarrier systems for the delivery of cytochrome C (CC). This system is based on an encapsulation protocol of the therapeutic protein into the polymer network. NGs were formed via inverse nanoprecipitation using inverse electron-demand Diels–Alder cyclizations (iEDDA) between methyl tetrazines and norbornenes. Coprecipitation of CC led to high encapsulation efficiencies. Applying physiological reductive conditions of l-glutathione (GSH) led to degradation of the nanogel network, releasing 80% of the loaded CC within 48 h while maintaining protein functionality. Cytotoxicity measurements revealed high potency of CC-loaded NGs for various cancer cell lines with low IC50 values (up to 30 μg·mL−1), whereas free polymer was well tolerated up to a concentration of 1.50 mg·mL−1. Confocal laser scanning microscopy (CLSM) was used to monitor internalization of free and CC-loaded NGs and demonstrate the protein cargo’s release into the cytosol

Fluorescent Polymer—Single‐Walled Carbon Nanotube Complexes with Charged and Noncharged Dendronized Perylene Bisimides for Bioimaging Studies

Fluorescent nanomaterials are expected to revolutionize medical diagnostic, imaging, and therapeutic tools due to their superior optical and structural properties. Their inefficient water solubility, cell permeability, biodistribution, and high toxicity, however, limit the full potential of their application. To overcome these obstacles, a water‐soluble, fluorescent, cytocompatible polymer—single‐walled carbon nanotube (SWNT) complex is introduced for bioimaging applications. The supramolecular complex consists of an alkylated polymer conjugated with neutral hydroxylated or charged sulfated dendronized perylene bisimides (PBIs) and SWNTs as a general immobilization platform. The polymer backbone solubilizes the SWNTs, decorates them with fluorescent PBIs, and strongly improves their cytocompatibility by wrapping around the SWNT scaffold. In photophysical measurements and biological in vitro studies, sulfated complexes exhibit superior optical properties, cellular uptake, and intracellular staining over their hydroxylated analogs. A toxicity assay confirms the highly improved cytocompatibility of the polymer‐wrapped SWNTs toward surfactant‐solubilized SWNTs. In microscopy studies the complexes allow for the direct imaging of the SWNTs' cellular uptake via the PBI and SWNT emission using the 1st and 2nd optical window for bioimaging. These findings render the polymer‐SWNT complexes with nanometer size, dual fluorescence, multiple charges, and high cytocompatibility as valuable systems for a broad range of fluorescence bioimaging studies

Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System

Biocompatible polymers with the ability to load and release a cargo at the site of action in a smart response to stimuli have attracted great attention in the field of drug delivery and cancer therapy. In this work, we synthesize a dual-responsive dendritic polyglycerol sulfate (DR-dPGS) drug delivery system by copolymerization of glycidol, ε-caprolactone and an epoxide monomer bearing a disulfide bond (SSG), followed by sulfation of terminal hydroxyl groups of the copolymer. The effect of different catalysts, including Lewis acids and organic bases, on the molecular weight, monomer content and polymer structure was investigated. The degradation of the polymer backbone was proven in presence of reducing agents and candida antarctica Lipase B (CALB) enzyme, which results in the cleavage of the disulfides and ester bonds, respectively. The hydrophobic anticancer drug Doxorubicin (DOX) was loaded in the polymer and the kinetic assessment showed an enhanced drug release with glutathione (GSH) or CALB as compared to controls and a synergistic effect of a combination of both stimuli. Cell uptake was studied by using confocal laser scanning microscopy with HeLa cells and showed the uptake of the Dox-loaded carriers and the release of the drug into the nucleus. Cytotoxicity tests with three different cancer cell lines showed good tolerability of the polymers of as high concentrations as 1 mg mL−1, while cancer cell growth was efficiently inhibited by DR-dPGS@Dox

One‐Pot Covalent Functionalization of 2D Black Phosphorus by Anionic Ring Opening Polymerization

In this work, a one‐pot approach for the covalent functionalization of few‐layer black phosphorus (BP) by anionic ring opening polymerization of glycidol to obtain multifunctional BP‐polyglycerol (BP‐PG) with high amphiphilicity for near‐infrared‐responsive drug delivery and biocompatibility is reported. Straightforward synthesis in combination with exceptional biological and physicochemical properties designates functionalized BP‐PG as a promising candidate for a broad range of biomedical applications