Evolution of Molecularly Imprinted Enzyme Inhibitors: From Simple Activity Inhibition to Pathological Cell Regulation.

Molecular imprinting represents one of the most promising strategies to design artificial enzyme inhibitors. However, the study of molecularly imprinted enzyme inhibitors (MIEIs) remains at a primary stage. Advanced applications of MIEIs for cell regulation have rarely been explored. Using a solid-phase oriented imprinting strategy so as to leave the active site of the enzymes accessible, we synthesized two MIEIs that exhibit high specificity and potent inhibitory effects (inhibition constant at low nM range) towards trypsin and angiogenin. The trypsin MIEI inhibits trypsin activity, tryptic digestion-induced extracellular matrix lysis and cell membrane destruction, indicating its utility in the treatment of active trypsin-dependent cell injury. The angiogenin MIEI blocks cancer cell proliferation by suppressing the ribonuclease activity of angiogenin and decreasing the angiogenin level inside and outside HeLa cells. Our work demonstrates the versatility of MIEIs for both enzyme inhibition and cell fate manipulation, showing their great potential as therapeutic drugs in biomedicine.

Molecularly Imprinted Synthetic Antibodies: From Chemical Design to Biomedical Applications.

Billions of dollars are invested into the monoclonal antibody market every year to meet the increasing demand in clinical diagnosis and therapy. However, natural antibodies still suffer from poor stability and high cost, as well as ethical issues in animal experiments. Thus, developing antibody substitutes or mimics is a long-term goal for scientists. The molecular imprinting technique presents one of the most promising strategies for antibody mimicking. The molecularly imprinted polymers (MIPs) are also called "molecularly imprinted synthetic antibodies" (MISAs). The breakthroughs of key technologies and innovations in chemistry and material science in the last decades have led to the rapid development of MISAs, and their molecular affinity has become comparable to that of natural antibodies. Currently, MISAs are undergoing a revolutionary transformation of their applications, from initial adsorption and separation to the rising fields of biomedicine. Herein, the fundamental chemical design of MISAs is examined, and then current progress in biomedical applications is the focus. Meanwhile, the potential of MISAs as qualified substitutes or even to transcend the performance of natural antibodies is discussed from the perspective of frontier needs in biomedicines, to facilitate the rapid development of synthetic artificial antibodies.

Typical Fluorescent Sensors Exploiting Molecularly Imprinted Hydrogels for Environmentally and Medicinally Important Analytes Detection.

In this work, two typical fluorescent sensors were generated by exploiting molecularly imprinted polymeric hydrogels (MIPGs) for zearalenone (ZON) and glucuronic acid (GA) detection, via the analyte's self-fluorescence property and receptor's fluorescence effect, respectively. Though significant advances have been achieved on MIPG-fluorescent sensors endowed with superior stability over natural receptor-sensors, there is an increasing demand for developing sensing devices with cost-effective, easy-to-use, portable advantages in terms of commercialization. Zooming in on the commercial potential of MIPG-fluorescent sensors, the MIPG_ZON is synthesized using zearalanone (an analogue of ZON) as template, which exhibits good detection performance even in corn samples with a limit of detection of 1.6 µM. In parallel, fluorescein-incorporated MIPG_GA is obtained and directly used for cancer cell imaging, with significant specificity and selectivity. Last but not least, our consolidated application results unfold new opportunities for MIPG-fluorescent sensors for environmentally and medicinally important analytes detection.

Thermo-responsive imprinted hydrogel with switchable sialic acid recognition for selective cancer cell isolation from blood.

In this work, a sialic acid (SA)-imprinted thermo-responsive hydrogel layer was prepared for selective capture and release of cancer cells. The SA-imprinting process was performed at 37 °C using thermo-responsive functional monomer, thus generating switchable SA-recognition sites with potent SA binding at 37 °C and weak binding at a lower temperature (e.g., 25 °C). Since SA is often overexpressed at the glycan terminals of cell membrane proteins or lipids, the SA-imprinted hydrogel layer could be used for selective cancer cell recognition. Our results confirmed that the hydrogel layer could efficiently capture cancer cells from not only the culture medium but also the real blood samples. In addition, the captured cells could be non-invasively released by lowing the temperature. Considering the non-invasive processing mode, considerable capture efficiency, good cell selectivity, as well as the more stable and durable SA-imprinted sites compared to natural antibodies or receptors, this thermo-responsive hydrogel layer could be used as a promising and general platform for cell-based cancer diagnosis.