Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays

We present a soft lithographic method to fabricate multiphenotype cell arrays by capturing cells within an array of reversibly sealed microfluidic channels. The technique uses reversible sealing of elastomeric polydimethylsiloxane (PDMS) molds on surfaces to sequentially deliver various fluids or cells onto specific locations on a substrate. Microwells on the substrate were used to capture and immobilize cells within low shear stress regions inside channels. By using an array of channels it was possible to deposit multiple cell types, such as hepatocytes, fibroblasts, and embryonic stem cells, on the substrates. Upon formation of the cell arrays on the substrate, the PDMS mold could be removed, generating a multiphenotype array of cells. In addition, the orthogonal alignment and subsequent attachment of a secondary array of channels on the patterned substrates could be used to deliver fluids to the patterned cells. The ability to position many cell types on particular regions within a two dimensional substrate could potentially lead to improved high-throughput methods applicable to drug screening and tissue engineering.     

Magnetic solid-phase extraction using Schiff base ligand supported on magnetic nanoparticles as sorbent combined with dispersive liquid-liquid microextraction for the extraction of phenols from water samples

ABSTRACT

In this work, the magnetic sorbent was developed by covalent binding of a Schiff base ligand, N,N’-bis(3-salicyliden aminopropyl)amine (salpr), on the surface of silica coated magnetic nanoparticles (Salpr@SCMNPs). The core-shell nanoparticle was applied for the magnetic solid-phase extraction (MSPE) combined with dispersive liquid-liquid microextraction (DLLME) of phenolic compounds from water samples prior to gas chromatography-flame ionisation detector (GC?FID). Characterisation of the Salpr@SCMNPs was performed with different physicochemical methods such as Fourier transform infrared (FT-IR), scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM). Variables affecting the performance of both extraction steps such as pH of the water sample, the sorbent amount, the desorption conditions, the extraction time; and extraction solvent were studied. Under the optimised conditions, the analytical performances were determined with a linear range of 0.01–100 ng mL^?1 and a limit of detection at 0.003–0.02 ng mL^?1 for all of the analytes studied. The intra-day (n = 5) and inter-day (n = 3) relative standard deviations (RSD%) of three replicates were each demonstrated in the range of 6.9–8.9% and 7.3–10.1%, respectively. The proposed method was executed for the analysis of real water samples, whereby recoveries in the range of 92.9–99.0% and RSD% lower than 6.1% were attained.     

Development of Multinuclear Polymeric Nanoparticles as Robust Protein Nanocarriers

One limitation of current biodegradable polymeric nanoparticles is their inability to effectively encapsulate and sustainably release proteins while maintaining protein bioactivity. Here we report the engineering of PLGA–polycation nanoparticles with a core–shell structure that act as a robust vector for the encapsulation and delivery of proteins and peptides. The optimized nanoparticles can load high amounts of proteins (>20 % of nanoparticles by weight) in aqueous solution without organic solvents through electrostatic interactions by simple mixing, thereby forming nanospheres in seconds with diameters <200 nm. The relationship between nanosphere size, surface charge, PLGA–polycation composition, and protein loading is also investigated. The stable nanosphere complexes contain multiple PLGA–polycation nanoparticles, surrounded by large amounts of protein. This study highlights a novel strategy for the delivery of proteins and other relevant molecules.     

One‐Pot Synthesis of Sulfonamides and Sulfonyl Azides from Thiols using Chloramine‐T

A convenient synthesis of sulfonamides and sulfonyl azides from thiols is described. In situ preparation of sulfonyl chlorides from thiols was accomplished by oxidation with chloramine‐T (=N‐chlorotosylamide=N‐chloro‐4‐methylbenzenesulfonamide), tetrabutylammonium chloride (Bu₄NCl), and H₂O. The sulfonyl chlorides were then further allowed to react with excess amine or NaN₃ in the same pot.     

Hydrophobic Cysteine Poly(disulfide)‐based Redox‐Hypersensitive Nanoparticle Platform for Cancer Theranostics

Selective tumor targeting and drug delivery are critical for cancer treatment. Stimulus‐sensitive nanoparticle (NP) systems have been designed to specifically respond to significant abnormalities in the tumor microenvironment, which could dramatically improve therapeutic performance in terms of enhanced efficiency, targetability, and reduced side‐effects. We report the development of a novel L ‐cysteine‐based poly (disulfide amide) (Cys‐PDSA) family for fabricating redox‐triggered NPs, with high hydrophobic drug loading capacity (up to 25 wt % docetaxel) and tunable properties. The polymers are synthesized through one‐step rapid polycondensation of two nontoxic building blocks: L ‐cystine ester and versatile fatty diacids, which make the polymer redox responsive and give it a tunable polymer structure, respectively. Alterations to the diacid structure could rationally tune the physicochemical properties of the polymers and the corresponding NPs, leading to the control of NP size, hydrophobicity, degradation rate, redox response, and secondary self‐assembly after NP reductive dissociation. In vitro and in vivo results demonstrate these NPs’ excellent biocompatibility, high selectivity of redox‐triggered drug release, and significant anticancer performance. This system provides a promising strategy for advanced anticancer theranostic applications.     

Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins

Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide‐ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self‐assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface‐coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin‐coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response.     

Engineering of lipid-coated PLGA nanoparticles with a tunable payload of diagnostically active nanocrystals for medical imaging

Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles that incorporate high payloads of nanocrystals into their core for tunable bioimaging features. We accomplished this through esterification reactions of PLGA to generate polymers modified with nanocrystals. The PLGA nanoparticles formed from modified PLGA polymers that were functionalized with either gold nanocrystals or quantum dots exhibited favorable features for computed tomography and optical imaging, respectively.