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Receptors are lipid bilayer‐resident molecules that perform a myriad of functions in a cell, from recognition to signaling and solute internalization, and are typically based on proteins. Herein, artificial receptors are engineered based on small organic molecules, toward chemical, non‐genetic engineering of cells. Specifically, artificial internalizing receptors are designed for selective targeting and cell‐specific drug delivery. The artificial receptors are shown to afford nanomolar potency of action for the cognate antibody‐drug conjugates. In the chemically engineered cells, the conjugate activity is at the same time more potent and significantly faster than that observed with the use of the pristine drug. In a mixed cell population, an antibody‐drug conjugate targeted to the artificial receptor can selectively eliminate the chemical receptor‐engineered cells. Taken together, these results illustrate that artificial receptors based on small organic molecules are simple by structure but can mediate one of the foundational cellular functions, namely endocytosis, with excellence. Most importantly, these receptors are truly bio‐orthogonal and thus afford a dedicated route of communication with the chemically engineered cells. [ABSTRACT FROM AUTHOR]

The treatment of implant‐associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic‐tolerant persister cells. This need is addressed herein through an engineering of antibody‐drug conjugates (ADCs) that contain an anti‐neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non‐specific counterpart, in suspension and within biofilms, in vitro, and in an implant‐associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms. [ABSTRACT FROM AUTHOR]

Adhesion underwater is a major challenge. Mussel‐inspired complex coacervates functionalized with L‐3,4‐dihydroxyphenylalanine (L‐DOPA) are proposed for underwater adhesives through versatile chemistry of DOPA, however, simple, efficient, controllable, and nontoxic procedures to harness them are still under investigation. In this study, inspired from the mussel byssus formation process, coacervate adhesives are formed underwater by simple injection of an acidic proto‐coacervate of DOPA functionalized polyelectrolytes on underwater surfaces. The proto‐coacervate is initially an acidic liquid, it increased in pH due to water diffusion, resulting in coacervation driven by electrostatic interaction, without the requirement for pH adjustment or organic solvents. Additionally, the pH of liquid–liquid phase separation is tuned by substituting polyelectrolytes with different pKa, which satisfied different pH requirement in real life. The coacervate‐based adhesives on glass substrates exhibit strengths comparable to commercial glues when dry and to mussel glue when wet, showing high biocompatibility in human epidermis in vitro. [ABSTRACT FROM AUTHOR]

The newest generation of cell‐based technologies relies heavily on methods to communicate to the engineered cells using artificial receptors, specifically to deactivate the cells administered to a patient in the event of adverse effects. Herein, artificial synthetic internalizing receptors are engineered that function in mammalian cells in 2D and in 3D and afford targeted, specific intracellular drug delivery with nanomolar potency in the most challenging cell type, namely primary, donor‐derived T cells. Receptor design comprises a lipid bilayer anchor for receptor integration into cell membrane and a small xenobiotic molecule as a recognition ligand. Artificial receptors are successfully targeted by the corresponding antibody–drug conjugate (ADC) and exhibit efficient cargo cell entry with ensuing intracellular effects. Receptor integration into cells is fast and robust and affords targeted cell entry in under 2 h. Through a combination of the receptor design and the use of ADC, combined benefits previously made available by chimeric artificial receptors (performance in T cells) and the chemical counterpart (robustness and simplicity) in a single functional platform is achieved. Artificial synthetic receptors are poised to facilitate the maturation of engineered cells as tools of biotechnology and biomedicine. [ABSTRACT FROM AUTHOR]