Sulfated Cellulose Nanofiber Hydrogel with Mucus-Like Activities for Virus Inhibition.

Mucus is the first defense barrier against viruses in the human immune system. Inspired by the mucus structure, we designed a highly sulfated hydrogel to bind viruses and prevent infection of the underlying cells. The hydrogel was formed by gelation of sulfated cellulose nanofiber (SCNF) with Ca.

Mucin-Inspired Polymeric Fibers for Herpes Simplex Virus Type 1 Inhibition.

Mucus lines the epithelial cells at the biological interface and is the first line of defense against multiple viral infections. Mucins, the gel-forming components of mucus, are high molecular weight glycoproteins and crucial for preventing infections by binding pathogens. Consequently, mimicking mucins is a promising strategy for new synthetic virus inhibitors.

Photo-responsive hydrogels based on a ruthenium complex: synthesis and degradation.

We report the synthesis of a photo responsive metallo-hydrogel based on a ruthenium(II) complex as a functional cross-linker. This metal complex contains reactive 4AAMP (= 4-(acrylamidomethyl)pyridine) ligands, which can be cleaved by light-induced ligand substitution. Ru[(bpy)(4AAMP)] cross-links 4-arm-PEG-SH macromonomers by thia-Michael-addition to the photocleavable 4AAMP ligand for the preparation of the hydrogel.

Synthesis of -symmetric star shaped amphiphiles for drug delivery applications.

-symmetric star-shaped aromatic compounds are known to possess unique characteristics which facilitate their industrial and biomedical applications. Herein, we report the design, synthesis, self-assembly and drug/dye delivery capabilities of -symmetric, hexa-substituted benzene-based amphiphiles. The synthesis of the hexa-substituted -symmetric core involves -acetylation of phloroglucinol to yield the corresponding tri-acetyl derivative.

Cell-Penetrating Peptide-Bismuth Bicycles.

Cell-penetrating peptides (CPPs) play a significant role in the delivery of cargos into human cells. We report the first CPPs based on peptide-bismuth bicycles, which can be readily obtained from commercially available peptide precursors, making them accessible for a wide range of applications. These CPPs enter human cells as demonstrated by live-cell confocal microscopy using fluorescently labelled peptides.

Esterase-Responsive Polyglycerol-Based Nanogels for Intracellular Drug Delivery in Rare Gastrointestinal Stromal Tumors.

Rare gastrointestinal stromal tumors (GISTs) are caused by mutations in the KIT and PDGFRA genes. Avapritinib (BLU-285) is a targeted selective inhibitor for mutated KIT and PDGFRA receptors that can be used to treat these tumors. However, there are subtypes of GISTs that exhibit resistance against BLU-285 and thus require other treatment strategies.

Dendritic Glycerol-Cholesterol Amphiphiles as Drug Delivery Systems: A Comparison between Monomeric and Polymeric Structures.

The application of micelles as drug delivery systems has gained a great deal of attention as a means to overcome the current several drawbacks present in conventional cancer treatments. In this work, we highlight the comparison of polymeric and monomeric amphiphilic systems with a similar hydrophilic-lipophilic balance (HLB) in terms of their biocompatibility, aggregation behavior in aqueous solution, and potential in solubilizing hydrophobic compounds. The polymeric system consists of non-ionic polymeric amphiphiles synthesized via sequential RAFT polymerization of polyglycerol first-generation [G1] dendron methacrylate and cholesterol methacrylate to obtain poly(G1-polyglycerol dendron methacrylate)-block-poly(cholesterol methacrylate) (pG1MA-b-pCMA).

Shell-sheddable dendritic polyglycerol sulfates loaded with sunitinib for inhibition of tumor angiogenesis.

Induced angiogenesis, a specific hallmark of cancer, plays a vital role in tumor progression and can be targeted by inhibitors like sunitinib. Sunitinib is a small hydrophobic molecule suffering from low bioavailability and a short half-life in the bloodstream. To overcome these drawbacks, suitable drug delivery systems need to be developed.

Benzoxaborole-grafted high molecular weight chitosan from prawn: Synthesis, characterization, target recognition and antibacterial properties.

Boronated polymers are in the focus of dynamic functional materials due to the versatility of the B-O interactions and accessibility of precursors. Polysaccharides are highly biocompatible, and therefore, an attractive platform for anchoring boronic acid groups for further bioconjugation of cis-diol containing molecules. We report for the first time the introduction of benzoxaborole by amidation of the amino groups of chitosan improving solubility and introducing cis-diol recognition at physiological pH.

Mucin-Inspired Single-Chain Polymer (MIP) Fibers as Potent SARS-CoV-2 Inhibitors.

Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin-inspired nanostructure, produced via a synthetic methodology to prepare methacrylate-based dendronized polysulfates (MIP-1) on a multi gram-scale with high molecular weight (MW=450 kDa) and thiol end-functionalized mucin-inspired polymer (MIP) via RAFT polymerization.

Fluorinated dendritic amphiphiles, their stomatosome aggregates and application in enzyme encapsulation.

Enzymes are more selective and efficient than synthetic catalysts but are limited by difficult recycling. This is overcome by immobilisation, namely through encapsulation, with the main drawback of this method being slow diffusion of products and reactants, resulting in effectively lowered enzyme activity. Fluorinated dendritic amphiphiles were reported to self-assemble into regularly perforated bilayer vesicles, so-called "stomatosomes".

Dendritic polyglycerolsulfate-SS-poly(ester amide) micelles for the systemic delivery of docetaxel: pushing the limits of stability through the insertion of π-π interactions.

Insufficient stability of micellar drug delivery systems is still the major limitation to their systematic application in chemotherapy. This work demonstrates novel π-electron stabilized polyelectrolyte block copolymer micelles based on dendritic polyglycerolsulfate-cystamine--poly(4-benzoyl-1,4-oxazepan-7-one)-pyrene (dPGS-SS-POxPPh-Py) presenting a very low critical micelle concentration (CMC) of 0.3 mg L (18 nM), 55-fold lower than that of conventional amphiphilic block copolymer micelles.

Bromo- and glycosyl-substituted BODIPYs for application in photodynamic therapy and imaging.

The introduction of heavy atoms into the BODIPY-core structure has proven to be a straightforward strategy for optimizing the design of such dyes towards enhanced generation of singlet oxygen rendering them suitable as photosensitizers for photodynamic therapy (PDT). In this work, BODIPYs are presented by combining the concept of bromination with nucleophilic aromatic substitution (SAr) of a pentafluorophenyl or a 4-fluoro-3-nitrophenyl moiety to introduce functional groups, thus improving the phototoxic effect of the BODIPYs as well as their solubility in the biological environment. The nucleophilic substitution enabled functionalization with various amines and alcohols as well as unprotected thiocarbohydrates.

Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants.

As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins.

Fabrication of hydrolase responsive diglycerol based Gemini amphiphiles for dermal drug delivery applications.

Since biocatalysts manoeuvre most of the physiological activities in living organisms and exhibit extreme selectivity and specificity, their use to trigger physicochemical change in polymeric architectures has been successfully used for targeted drug delivery. Our major interest is to develop lipase responsive nanoscale delivery systems from bio-compatible and biodegradable building blocks. Herein, we report the synthesis of four novel non-ionic Gemini amphiphiles using a chemo-enzymatic approach.

Polyanionic Amphiphilic Dendritic Polyglycerols as Broad-Spectrum Viral Inhibitors with a Virucidal Mechanism.

Heparin has been known to be a broad-spectrum inhibitor of viral infection for almost 70 years, and it has been used as a medication for almost 90 years due to its anticoagulant effect. This nontoxic biocompatible polymer efficiently binds to many types of viruses and prevents their attachment to cell membranes. However, the anticoagulant properties are limiting their use as an antiviral drug.

One-pot gram-scale synthesis of virucidal heparin-mimicking polymers as HSV-1 inhibitors.

A straightforward and gram-scale synthesis method was developed to engineer highly sulfated hyperbranched polyglycerol bearing sulfated alkyl chains. The compounds with shorter alkyl chains showed multivalent virustatic inhibition against herpes simplex virus type 1 (HSV-1), similar to heparin. In contrast, the compound with the longest alkyl chains irreversibly inhibited the virus.

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).

Biodegradable Dendritic Polyglycerol Sulfate for the Delivery and Tumor Accumulation of Cytostatic Anticancer Drugs.

Targeted delivery and extended blood circulation of anticancer drugs have been the challenges for decreasing the adverse side effects and improving the therapeutic efficiency in cancer chemotherapy. Herein, we present a drug delivery system (DDS) based on biodegradable dendritic polyglycerol sulfate-bearing poly(caprolactone) (dPGS-PCL) chains, which has been synthesized on 20 g scale using a straightforward two-step protocol. fluorescence imaging demonstrated a significant accumulation of the DDS in the tumor environment.

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.

Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures.

Inhibition of herpes simplex virus type 1 (HSV-1) binding to the host cell surface by highly sulfated architectures is among the promising strategies to prevent virus entry and infection. However, the structural flexibility of multivalent inhibitors plays a major role in effective blockage and inhibition of virus receptors. In this study, we demonstrate the inhibitory effect of a polymer scaffold on the HSV-1 infection by using highly sulfated polyglycerols with different architectures (linear, dendronized, and hyperbranched).

Newer Non-ionic A B -Type Enzyme-Responsive Amphiphiles for Drug Delivery.

A new series of nonionic gemini amphiphiles have been synthesized in a multi-step chemoenzymatic approach by using a novel A B -type central core consisting of conjugating glycerol and propargyl bromide on 5-hydroxy isophthalic acid. A pair of hydrophilic monomethoxy poly(ethylene glycol) (mPEG) and hydrophobic linear alkyl chains (C /C ) were then added to the core to obtain amphiphilic architectures. The aggregation tendency in aqueous media was studied by dynamic light scattering, fluorescence spectroscopy and cryogenic transmission electron microscopy.

Graphene Sheets with Defined Dual Functionalities for the Strong SARS-CoV-2 Interactions.

Search of new strategies for the inhibition of respiratory viruses is one of the urgent health challenges worldwide, as most of the current therapeutic agents and treatments are inefficient. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic and has taken lives of approximately two million people to date. Even though various vaccines are currently under development, virus, and especially its spike glycoprotein can mutate, which highlights a need for a broad-spectrum inhibitor.

Oligo-glycerol based non-ionic amphiphilic nanocarriers for lipase mediated controlled drug release.

A new class of non-ionic amphiphiles is synthesized using a diaryl derivative of diglycerol as a central core and functionalizing it with long alkyl chains (C-12/C-15) and monomethoxy PEG moiety ( : 350/550) by following a chemo-enzymatic approach. The aggregation behavior of the amphiphiles in aqueous medium is studied by using dynamic light scattering (DLS) and fluorescence spectroscopy, whereas the size and morphology of the aggregates are studied by transmission electron microscopy (TEM). A hydrophobic dye, Nile red and a hydrophobic drug, nimodipine, are used to demonstrate the nano-carrier capability of these non-ionic amphiphilic systems and the results are compared with amphiphilic analogues obtained from the triaryl derivatives of triglycerol.