Molecularly imprinted polymers (MIPs) have been widely used in nanomedicine during the last few years. However, their potential is limited by their intrinsic properties resulting, for instance, in lack of control in drug release processes or complex detection for in vivo imaging. Recent attempts in creating hybrid nanomaterials combining MIPs with inorganic nanomaterials succeeded in providing a wide range of new interesting properties suitable for nanomedicine. Through this review, we aim to illustrate how hybrids molecularly imprinted polymers may improve patient care with enhanced imaging, treatments and combination of both.

The illicit use of fentanyl has led to hundreds of thousands of opioid-related deaths worldwide. Therefore, the detection of fentanyl by law enforcement and recreational users is of utmost importance. However, current detection methods are expensive, time-consuming, require special storage conditions and necessitate complex instrumentation that is generally unportable and requires skilled personnel to operate. An alternative approach would be using molecularly imprinted polymers (MIPs) as the recognition component of a handheld sensor, testing strip, or color-based assay. In this work, a molecularly imprinted polymer was made by using methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) as the functional monomer and cross-linking monomer respectively, and benzylfentanyl (Bfen) as the template. The use of benzylfentanyl is advantageous because it closely resembles the structure of fentanyl but does not have any physiological effects as a narcotic. Important studies herein determined the optimum ratio of the template:functional monomer, with subsequent evaluations of selectivity versus the commonly encountered narcotics such as heroin, cocaine, and methamphetamine. The data obtained from the HPLC analysis showed that the Bfen-MIP was successful in selectively binding the template and actual fentanyl, better than other common narcotics.

In this work, we firstly explored a mild, clean, and highly efficient approach for the synthesis of graphene quantum dots (GQDs). GQDs with carboxyl groups or amino groups, were prepared from one-pot environmentally friendly method assisted by hydrogen peroxide, respectively. It was proved that carboxyl groups played an important role in the fluorescence quenching. Based on these findings, we developed a novel fluorescent nanosensor by combining molecularly imprinted polymers (MIPs) with carboxyl functionalized GQDs for the determination of tetracycline (TC) in aqueous samples. The nanocomposite was prepared using a sol-gel process. GQDs-MIPs showed strong fluorescent emission at 410 nm when excited at 360 nm, which was subsequently quenched in the presence of TC. Under optimum conditions, the fluorescence intensity of GQDs-MIPs decreased in response to the increase of TC concentration with good linearity rage of 1.0-104 µg L-1. The limit of detection was determined to be 1 µg L-1. The fluorescence intensity of GQDs-MIPs was more strongly quenched by TC compared to the corresponding non-imprinted polymers, GQDs-NIPs. With the high sensitivity, the material was also successfully worked for the detection of TC in real spiked milk samples.

Molecularly imprinted polymers (MIPs) were synthesized and applied for the selective extraction of oblongifolin C (OC) from fruit extracts of Garcinia yunnanensis Hu. A series of experiments and computational approaches were employed to improve the efficiency of screening for optimal MIP systems in the study. The molar ratio (1:4) was chosen at last based on the comparison of the binding energy of the complexes between the template (OC) and functional monomers using density functional theory (DFT) at the RI-PBE-D3-gCP/def2-TZVP level of theory. The binding characterization and the molecular recognition mechanism of MIPs were further explained using the molecular modeling method and NMR and IR spectra data. The reusability of this approach was demonstrated in over 20 batch rebinding experiments. 140.5 mg of OC (>95% purity) was obtained from the 5 g extracts with 2 g of MIPs with the best binding properties through gradient elution program from 35% to 70% methanol-water solution. At the same time, another structural analog, 46.5 mg of guttiferone K (GK) (>88% purity), was also obtained by the gradient elution procedure. Our results showed that the structural analogs could be separated from the crude extracts by the molecularly imprinted solid-phase extraction (MISPE) using a gradient elution procedure for the first time.

This paper presents the development of a cheap and rapid electrochemical sensor for ascorbic acid detection. In particular, the graphite ink working electrode of screen-printed cells was covered by a film of elecrosynthesized molecularly imprinted polypyrrole (e-MIP); differential pulse voltammetry (DPV) was the selected method for the analyte detection. The ascorbic acid molecules were suc-cessfully entrapped in the polypyrrole film, creating the recognition sites. The best results were obtained after polypyrrole overoxidation and performing the measurements in phosphate buffer solution 0.05 M/KCl 0.1M at pH 7.5. The comparison with the bare and the not imprinted polypyrrole-modified electrodes showed the highest selectivity and reproducibility of the e-MIP-based sensor. The developed method was applied to assess ascorbic acid in farmaceutical products obtaining values not significantly different from the declared content.

The rapid, sensitive, and selective detection of pathogenic bacteria is of utmost importance in ensuring food safety and preventing the spread of infectious diseases. Here, we present a novel, reusable, and cost-effective impedimetric sensor based on a dual bacteria-imprinted polymer (DBIP) for the specific detection of Escherichia coli O157:H7 and Staphylococcus aureus. The DBIP sensor stands out with its remarkably short fabrication time of just 20 minutes, achieved through the efficient electro-polymerization of o-phenylenediamine monomer in the presence of dual bacterial templates, followed by in-situ template removal. The key structural feature of the DBIP sensor lies in the cavity-free imprinting sites, indicative of a thin layer of bacterial surface imprinting. This facilitates rapid rebinding of the target bacteria within a mere 15 minutes, while the sensing interface regenerates in just 10 minutes, enhancing the sensor's overall efficiency. A notable advantage of the DBIP sensor is its exceptional selectivity, capable of distinguishing the target bacteria from closely related bacterial strains, including different serotypes. Moreover, the sensor exhibits high sensitivity, showcasing a low detection limit of approximately 9 CFU mL-1. The sensor's reusability further enhances its cost-effectiveness, reducing the need for frequent sensor replacements. The practicality of the DBIP sensor was demonstrated in the analysis of real apple juice samples, yielding good recoveries. The integration of quick fabrication, high selectivity, rapid response, sensitivity, and reusability makes the DBIP sensor a promising solution for monitoring pathogenic bacteria, playing a crucial role in ensuring food safety and safeguarding public health.

This mini-review critically summarizes the knowledge of imprinted polymer-based electrochemical sensors, for the detection of pesticides, metal ions and waterborne pathogenic bacteria, focusing on the period the last 5 years (citation of 78 papers published in 2017-2021, ie 63% of total citations). MIP-based electrochemical sensors exhibit low limit of detection, high selectivity, high sensitivity and low cost. Herein, we focused on the timely topics of water pollution by organics, inorganics and micro-organisms represented by pesticides, metal ions and bacteria, respectively. We put the emphasis on the design of imprinted polymers and their composites and coatings by radical polymerization, oxidative polymerization of conjugated monomers or sol-gel chemistry. Whilst most imprinted polymers are used in conjunction with differential pulse or square wave voltammetry for sensing organics and metal ions, electrochemical impedance spectroscopy (EIS) appears as the chief technique for detecting bacteria. This successful combination of EIS and imprinting technology should be harnessed in the coming years in the case of bacteria. Interestingly, bacteria are not always probed by bacteria-imprinted polymers; we report here their detection by monitoring specific (macro)molecules that reflect bacterial activity, for example quorum sensing signaling molecules or flagella proteins. If much has been developed in the past decade with glassy carbon or gold electrodes, it is clear that carbon paste electrodes of imprinted polymers are more and more investigated due to their versatility. Shortlisted case studies were critically reviewed and discussed; clearly a plethora of tricky strategies of designing selective electrochemical sensors are offered to “Imprinters”. We anticipate this review will be of interest to experts and new comers in the field who are paying time and effort combining electrochemical sensors with MIP technology.

A biomimetic, ion-imprinted polymer (IIP) was prepared by electropolymerization of pyrrole at the surface of gold electrodes decorated with vertically grown ZnO nanorods. The vertical growth of the nanorods was achieved via an ultrathin aryl monolayer grafted by reduction of diazonium salt precursor. Pyrrole was polymerized in the presence of L-cysteine as chelatant agent and Hg(II) (template). Hg(II)-imprinted polypyrrole (PPy) was also prepared on bare gold electrode in order to compare the two methods of sensor design (Au-ZnO-IIP vs Au-IIP). Non-imprinted PPy was prepared in the same conditions, however in the absence of any Hg2+ template. The strategy combining diazonium salt modification and ZnO nanorod decoration of gold electrodes permitted to increase considerably the specific surface and thus to improve the sensor performances. The limit of detection (LOD) of the designed sensor was ~1 pM, the lowest value ever reported in literature. The dissociation constants between PPy and Hg2+ were estimated at [Kd1 = (7.89 ± 3.63) mM and Kd2 = (38.10 ± 9.22) pM]. The sensitivity of the designed sensor was found to be 0.692 ± 0.034 μA/pM. The Au-ZnO-IIP was found to be highly selective towards Hg(II) compared to cadmium, lead and copper ions. This sensor design strategy could open up new horizons in monitoring toxic heavy metal ions in water and therefore contribute to enhance environmental quality.

There is an urgent demand worldwide for the development of highly selective adsorbents and sensors of heavy metal ions and other organic pollutants. Within these environmental and public health frameworks, we are combining the salient features of clays and chelatant polymers to design selective metal ion adsorbents. Towards this end, the ion imprinting approach has been used to develop a novel nanohybrid material for the selective separation of Cu2+ ions in aqueous solution. The Cu2+-imprinted polymer/ montmorillonite nanocomposite (IIP/Mt) and non-imprinted polymer/montmorillonite nanocomposite (NIP/Mt) were prepared by radical photopolymerization process in the visible light. Ion imprinting was indeed important as the recognition of copper ions by IIP/Mt was significantly superior to that of NIP/Mt that is the nanocomposite synthesized in the same way but in the absence of Cu2+ ions. The adsorption process as batch study was investigated under the experimental condition affecting same parameters such as contact time, concentration of ions metals and pH. The adsorption capacity of Cu2+ ions is maximized at pH 5. Removal of Cu2+ ion achieved equilibrium within 15 minutes; the results obtained were found to be fitted by the pseudo-second order kinetics model. The equilibrium process was well described by the Langmuir isothermal model and the maximum adsorption capacity was found to be 23.6 mg/g.

An interdigitated electrode sensor was designed and microfabricated for measuring the changes in the capacitance of three phosphate selective molecularly imprinted polymer (MIP) formulations, in order to provide hydroponics users with a portable nutrient sensing tool. The MIPs investigated were synthesised using different combinations of the functional monomers methacrylic acid (MAA) and N-allylthiourea, against the template molecules diphenyl phosphate, triethyl phosphate and trimethyl phosphate. A cross-interference study between phosphate, nitrate and sulfate was carried out for the MIP materials using an inductance, capacitance and resistance (LCR) meter. Capacitance measurements were taken applying an alternating current (AC) with a potential difference of 1 V root mean square (RMS) at a frequency of 1 kHz. The cross-interference study demonstrated a strong binding preference to phosphate over the other nutrient salts tested for each formulation. The size of template molecule and length of the functional monomer side groups also determined that a combination of a short chain functional monomer in combination with a template containing large R-groups produced the optimal binding site conditions when synthesising a phosphate selective MIP.

Parkinson’s Disease (PD) is a debilitating neurodegenerative disease, causing loss of motor function, and in some instances, cognitive decline and dementia, in those affected. The quality of life can be improved, and disease progression delayed through early interventions, however, current methods of confirming a PD diagnosis are extremely invasive. This prevents their use as a screening tool for the early onset stages of PD. We propose a surface imprinted polymer (SIP) electroimpedance spectroscopy (EIS) biosensor for detecting α-Synuclein (αSyn) and its aggregates, a biomarker that appears in saliva and blood during the early stages of PD as the blood brain barrier degrades. The surface imprinted polymer stamp is fabricated by low temperature melt stamping polycaprolactone (PCL) on interdigitated EIS electrodes. The result is a low-cost, small footprint biosensor that is highly suitable for non-invasive monitoring of the disease biomarker. The sensors were tested with αSyn dilutions in deionized water, and in constant ionic concentration matrix solutions with decreasing concentrations of αSyn to remove the background effects of concentration. The device response confirmed the specificity of these devices to the target protein of monomeric αSyn. The sensor limit of detection was measured to be 5 pg/L and its linear detection range was 5 pg/L – 5 µg/L. This covers the physiological range of αSyn in saliva and makes this a highly promising method of quantifying αSyn monomers for PD patients in the future. The SIP surface was regenerated, and the sensor reused to demonstrate its capability for repeat sensing as a potential continuous monitoring tool for the disease biomarker.

The chiral recognition of enantiomers is a topic of great importance. In this study, a straightforward and effective chiral detection strategy was developed for distinguishing between tryptophan (TRP) enantiomers. The approach involved the preparation of a magnetic molecularly imprinted chitosan (MMIC) for the sample preparation, which was combined with a nitrocellulose membrane (paper-based analytical device, PAD) integrated with D-TRP covalently-grafted polymethacrylic acid (PAD_PMA_D-TRP). The discrimination between TRP enantiomers was achieved using AuNPs as a colorimetric probe. Indeed, the presence of D-TRP rapidly induced the aggregation of AuNPs due to its strong affinity to PAD-PMA_D-TRP, resulting in a noticeable color change of the AuNPs from red to purple. On the other hand, L-TRP did not induce any color change. The chiral analysis could be easily performed with the naked eye and/or a smartphone. The developed method exhibited a detection limit of 3.3 µM and it was successfully applied to detect D-TRP in serum samples, demonstrating good recovery rates. The proposed procedure is characterized by its simplicity, cost-effectiveness, rapidity, and ease of operation.

The past two decades have witnessed the introduction of and then a steady increase in the use of computational techniques in the study and development of molecularly imprinted polymers (MIPs). Molecular dynamics (MD) based studies have had a significant role in this development as they can provide insights concerning the mechanisms governing the molecular level events underlying MIP synthesis and MIP-ligand interactions and can be used for the identification of preferred monomer compositions and for the prediction of MIP properties. We here review the role that MD has played in the development of molecular imprinting and examine the different types of MD strategies that have been used, including their advantages and challenges. Recent trends in the application of MD to the study of MIPs are presented, along with a perspective on the future importance of MD-based studies for the development of molecular imprinting science and technology.

The feasible, reliable and selective multi-template molecularly imprinted polymers (MT-MIPs) based on SBA-15 (SBA-15@MT-MIPs) for the selective separation and determination of the trace level of ginsenoside Rb₁ (Rb₁), ginsenoside Rg₁ (Rg₁) and notoginsenoside R₁ (R₁) (Panax notoginseng saponins, PNS) from biological samples were developed. The polymers were constructed by SBA-15 as support, Rb₁, Rg₁, R₁ as multi-template, acrylamide (AM) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker. The new synthetic SBA-15@MT-MIPs were satisfactorily applied to solid-phase extraction (SPE) coupled with high performance liquid chromatography (HPLC) for the separation and determination of trace PNS in plasma samples. Under the optimized conditions, the limits of detection (LODs) and quantitation (LOQs) of the proposed method for Rb₁, Rg₁ and R₁ were in the range of 0.63-0.75 ng mL^-1 and 2.1-2.5 ng mL^-1, respectively. The recoveries of R₁, Rb₁ and Rg₁ were obtained between 93.4% and 104.3% with relative standard deviations (RSDs) in the range of 3.3-4.2%. All results show that the obtained SBA-15@MT-MIPs could be a promising prospect for the practical application in the selective separation and enrichment of trace PNS in the biological samples.

Programmed cell death protein 1 (PD-1) is a biomarker on the surface of cells that has a role in promoting self-tolerance by suppressing the inflammatory activity of T cells. In this work, one peptide of PD-1 was used as the template in molecular imprinting. The magnetic peptide-imprinted poly(ethylene-co-vinyl alcohol) composite nanoparticles (MPIP NPs) were characterized by dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), Brunauer-Emmett-Teller (BET) analysis and superconducting quantum interference device (SQUID) analysis. Natural killer-92 (NK-92) cells were added to these composite nanoparticles and then incubated with human hepatoma (HepG2) cells. The viability and apoptosis pathway of HepG2 were then studied using cell counting kit-8 (CCK8) and the quantitative real-time polymerase chain reaction (qRT-PCR), respectively. These nanoparticles were found significantly enhance the activity of natural killer cells toward HepG2 cells by increasing expression of NK-kB, caspase 8 and especially caspase 3.

The method for quantitative analysis is based on the direct measurement of the analyte using differential pulse voltammetry (DPV), exploiting its oxidation peak. Calibration curves are set up to evaluate the figures of merit of the analytical method (LOD, LOQ, linear range). The application of the sensor for the dosing of GA in real matrices is carried out by analyzing non-alcoholic and alcoholic beverages and comparing the results with those reported in the literature and with the content of total polyphenols determined by the Folin-Ciocalteu method. In all cases, concentrations of GA align with those previously found in the literature for the beverages examined. Moreover, the values are always lower than the total polyphenols content; this demonstrates the good selectivity of the sensor that can discriminate the target molecule from other polyphenols present.