Search for: All records

The lack of suitable tools for the identification of potential drug leads from complex matrices is a bottleneck in drug discovery. Here, we report a novel method to screen complex matrices for new drug leads targeting transmembrane receptors. Using α 3 β 4 nicotinic receptors as a model system, we successfully demonstrated the ability of this new tool for the specific identification and effective extraction of binding compounds from complex mixtures. The formation of cell-membrane coated nanoparticles was confirmed by transmission electron microscopy. In particular, we have developed a direct tool to evaluate the presence of functional α 3 β 4 nicotinic receptors on the cell membrane. The specific ligand binding to α 3 β 4 nicotinic receptors was examined through ligand fishing experiments and confirmed by high-performance liquid chromatography coupled with diode-array detection and electrospray ionization mass spectrometry. This tool has a great potential to transform the drug discovery process focusing on identification of compounds targeting transmembrane proteins, as more than 50% of all modern pharmaceuticals use membrane proteins as prime targets. 

Although imaging‐guided drug delivery represents a noninvasive alternative to both surgical resection and systemic methods, it has seen limited clinical use due to the potential toxicity and fast clearance of currently available imaging agents. Herein, we introduce theranostic biocompatible microcapsules as efficient contrast‐enhanced imaging agents that combine magnetic resonance imaging (MRI) with ultrasound‐triggered drug release for real‐time tracking and targeted delivery in vivo. The 3‐μm diameter capsules are assembled via layer‐by‐layer deposition of the natural polyphenol tannic acid and poly(N‐vinylpyrrolidone) with 4 nm iron oxide nanoparticles incorporated in the capsule wall. The nanoparticle‐modified capsules exhibit excellent T₁and T₂MRI contrast in a clinical 3T MRI scanner. Loaded with the anticancer drug doxorubicin, these capsules circulate in the blood stream for at least 48 h, which is a remarkable improvement compared to nonencapsulated nanoparticles. The application of focused ultrasound results in targeted drug release with a 16‐fold increase in doxorubicin localization in tumors compared to off‐target organs in a mouse model of breast cancer. Owing to the active contrast, long circulation, customizable size, shape, composition, and precise delivery of high payload concentrations, these materials present a powerful and safe platform for imaging‐guided precision drug delivery.