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Drug targeting is a methodology that helps to overcome the side effects of therapeutic molecules. However, insufficient targeting specificity and the on-target/off-site delivery leave much room for improvement in the targeting endeavors. One approach to enhance the specificity of drug targeting is to engineer artificial receptors with recognition ligands not observed in nature. To this end, artificial internalizing receptors that feature cholesterylamine as the artificial pull-in mechanism, and an anti-fluorescein antibody as the exofacial recognition and capture tool are developed. Fluorescein labeling is among the most routine techniques in biochemistry and can readily provide a way to make cognate derivatives for receptor-mediated endocytosis using these artificial receptors. Herein, the synthesis and the structure-activity relationship for these artificial receptors are detailed, their potency and efficacy in mediating drug delivery for the antibody-drug conjugates are illustrated, and the scope and limitations of targeting the chemically engineered cells via artificial receptors are investigated. Taken together, the presented data explore an innovative approach to drug targeting and contribute to the development of techniques in cell engineering using the tools of chemistry., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

MicroRNAs (miRNAs) have emerged as promising diagnostic biomarkers and therapeutic targets in various diseases. However, there is currently a lack of molecular strategies that can effectively use disease-associated extracellular miRNAs as input signals to drive therapeutic functions. Herein, we present a modular and programmable miRNA-responsive chimeric DNA receptor (miRNA-CDR) capable of biomarker-driven therapy. By grafting a miRNA-responsive DNA nanodevice on a natural membrane receptor via aptamer anchoring, miRNA-CDR can sense extracellular miRNA levels and autonomously induce dimerization-mediated receptor activation via the complementary-mediated strand displacement reaction-induced dynamic DNA assembly. The sequence programmability of miRNA-CDR allows it to sense and respond to a user-defined miRNA with tunable sensitivity. Moreover, the miRNA-CDR is versatile and customizable to reprogram desirable signaling output via adapting a designated receptor, such as MET and FGFR1. Using a mouse model of drug-induced acute liver injury (DILI), we demonstrate the functionality of a designer miRNA-CDR in rewiring the recognition of the DILI-elevated miR-122 to promote MET signaling of hepatocytes for biomarker-driven in situ repair and liver function restoration. Our synthetic miRNA-CDR platform provides a novel molecular device enabling biomarker-driven therapeutic cellular response, potentially paving the way for improving the precision of cell therapy in regenerative medicine., (© 2023 Wiley-VCH GmbH.)

In the study, we have developed an efficient and robust method using dual modes of fluorescence sensing and smartphone readout for the detection of pyrethroids using artificial receptors inside a covalent organic framework. Carbazole-conjugated frameworks (CCFs) were used to prepare efficient fluorescent probes that combine stability with light-emitting activity. CN linkages between aldehydes and amines formed Schiff bases, allowing the development of layered structures, creating exceptionally stable frameworks. Artificial receptors that can bind compounds inside the CCFs with high affinity, for both the detection and absorption of λ-cyhalothrin (LC), were constructed using room-temperature reverse microemulsion polymerization. Under optimum conditions, the fluorescence sensing correlation with the concentration of LC showed good linearity in the range of 0.8-175 μg L -1 with a detection limit of 0.368 μg L -1 . The smartphone-based visible readout exhibited a good effect, with a detection limit of 4.067 μg L -1 , and recovery of 88 %-103% in food samples. A parallel analysis in food samples was conducted by high-performance liquid chromatography, the results showed good consistency, indicating the practicability of the developed method. Dual mode analysis can avoid the disadvantages of a single response, providing excellent sensitivity, specificity, and efficiency through a strong binding force between the target and the artificial receptors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The design of a fully synthetic, chemical "apoptosis-inducing receptor" (AIR) molecule is reported that is anchored into the lipid bilayer of cells, is activated by the incoming biological input, and responds with the release of a secondary messenger-a highly potent toxin for cell killing. The AIR molecule has four elements, namely, an exofacial trigger group, a bilayer anchor, a toxin as a secondary messenger, and a self-immolative scaffold as a mechanism for signal transduction. Receptor installation into cells is established via a robust protocol with minimal cell handling. The synthetic receptor remains dormant in the engineered cells, but is effectively triggered externally by the addition of an activating biomolecule (enzyme) or in a mixed cell population through interaction with the surrounding cells. In 3D cell culture (spheroids), receptor activation is accessible for at least 5 days, which compares favorably with other state of the art receptor designs., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Artificial receptor-based protein assays have various attractive features such as a long-term stability, a low-cost production process, and the ease of tuning the target specificity. However, such protein sensors are still immature compared with conventional immunoassays. To enhance the application potential of synthetic sensing materials, organic field-effect transistors (OFETs) are some of the suitable platforms for protein assays because of their solution processability, durability, and compact integration. Importantly, OFETs enable the electrical readout of the protein recognition phenomena of artificial receptors on sensing electrodes. Thus, we believe that OFETs functionalized with artificial protein receptors will be a powerful tool for the on-site analyses of target proteins. In this Minireview, we summarize the recent progress of the OFET-based protein assays including the rational design strategies for devices and sensing materials., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Synthetic sensing materials (artificial receptors) are some of the most attractive components of chemical/biosensors because of their long-term stability and low cost of production. However, the strategy for the practical design of these materials toward specific molecular recognition in water is not established yet. For the construction of artificial material-based chemical/biosensors, the bottom-up assembly of these materials is one of the effective methods. This is because the driving forces of molecular recognition on the receptors could be enhanced by the integration of such kinds of materials at the 'interfaces', such as the boundary portion between the liquid and solid phases. Additionally, the molecular assembly of such self-assembled monolayers (SAMs) can easily be installed in transducer devices. Thus, we believe that nanosensor platforms that consist of synthetic receptor membranes on the transducer surfaces can be applied to powerful tools for high-throughput analyses of the required targets. In this review, we briefly summarize a comprehensive overview that includes the preparation techniques for molecular assemblies, the characterization methods of the interfaces, and a few examples of receptor assembly-based chemical/biosensing platforms on each transduction mechanism.

Highly efficient transmembrane transport of exogenous reagents into cells is of vital importance for developing drug-delivery systems. Conventionally, transmembrane transport of exogenous reagents was accomplished with the assistance of transfection agents or other artificial means. However, the high toxicity and low transport efficiency of current delivery techniques still remain to be solved. In this work, by anchoring artificial receptors onto cell membranes with a mild chemical reaction, we demonstrated that the exogenous reagent framework nucleic acids, namely tetrahedral DNA nanostructures (TDN) can bind onto cell membranes effectively by the hybridization between single-stranded DNA (ssDNA) and pendant ssDNA of TDN. The transport rate was greatly enhanced, with the endocytosis time could be as fast as 0.5 h. Furthermore, the transport quantity was prominently improved, with around 30 % of TDN endocytosed within 4 h. Owing to its rapid transmembrane transport speed and improved endocytosis quantity, this artificial-receptor-mediated transmembrane transport is a promising tool for achieving rapid and highly efficient transmembrane transport of exogenous reagents., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work, surface magnetic molecularly imprinted polymers (SMMIPs) were synthesized and used as artificial receptors in the dispersive magnetic solid phase extraction (DMSPE) for capturing potential neuronal nitric oxide synthase-post synaptic density protein-95 (nNOS-PSD-95) uncouplers, which is known as neuroprotection against stroke. Factors that affected selective separation and adsorption of the artificial receptors, such as the amount of template, the types of functional monomer and porogen solvents, and the molar ratio of template/functional monomer/cross-linker were optimized. The artificial receptors were also characterized using fourier transformed infrared, scanning electron microscope, thermal gravimetric analysis and physical property measurement systems. Multiple interactions between template and SMMIPs led to larger binding capacities, faster binding kinetics, quicker separation abilities and more efficient selectivity than the surface magnetic nonimprinted polymers (SMNIPs). The SMMIPs were successfully applied to capture potential nNOS-PSD-95 uncouplers from complex samples, and eight compounds were seized and confirmed rapidly when combined with HPLC and MS. The detection of the new nNOS-PSD-95 uncouplers ranged from 0.001 to 1.500 mg/mL with correlation coefficients of 0.9990-0.9995. The LOD and LOQ were 0.10-0.68 μg/mL and 0.47-2.11 μg/mL, respectively. The neuroprotective effect and co-immunoprecipitation test in vitro revealed that Emodin-1-O-β-d-glucoside, Rhaponticin, Gnetol and 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside have neuroprotective and uncoupling activities, and that they may be the new uncouplers of nNOS-PSD-95., (Copyright © 2018 Elsevier B.V. All rights reserved.)