Glycan-specific molecularly imprinted polymers towards cancer diagnostics: merits, applications, and future perspectives.

Aberrant glycans are a hallmark of cancer states. Notably, emerging evidence has demonstrated that the diagnosis of cancers with tumour-specific glycan patterns holds great potential to address unmet medical needs, especially in improving diagnostic sensitivity and selectivity. However, despite vast glycans having been identified as potent markers, glycan-based diagnostic methods remain largely limited in clinical practice. There are several reasons that prevent them from reaching the market, and the lack of anti-glycan antibodies is one of the most challenging hurdles. With the increasing need for accelerating the translational process, numerous efforts have been made to find antibody alternatives, such as lectins, boronic acids and aptamers. However, issues concerning affinity, selectivity, stability and versatility are yet to be fully addressed. Molecularly imprinted polymers (MIPs), synthetic antibody mimics with tailored cavities for target molecules, hold the potential to revolutionize this dismal progress. MIPs can bind a wide range of glycan markers, even those without specific antibodies. This capacity effectively broadens the clinical applicability of glycan-based diagnostics. Additionally, glycoform-resolved diagnosis can also be achieved through customization of MIPs, allowing for more precise diagnostic applications. In this review, we intent to introduce the current status of glycans as potential biomarkers and critically evaluate the challenges that hinder the development of in vitro diagnostic assays, with a particular focus on glycan-specific recognition entities. Moreover, we highlight the key role of MIPs in this area and provide examples of their successful use. Finally, we conclude the review with the remaining challenges, future outlook, and emerging opportunities.

A molecularly imprinted photoelectrochemical sensor based on an rGO/MoSSe heterojunction for the detection of chlortetracycline.

A reduced graphene oxide/molybdenum selenosulfide (rGO/MoSSe) heterojunction was synthesized, and a molecularly imprinted photoelectrochemical sensor for the detection of chlortetracycline was prepared. MoSSe was grown in situ on rGO by a hydrothermal method to form an rGO/MoSSe heterojunction, which acts as the sensitive film of the sensor. Since rGO can promote electron transfer and effectively inhibit electron-hole recombination, it effectively reduces the recombination probability of electrons and holes and improves the photoelectric efficiency, thus enhancing the detection sensitivity of the PEC sensor. The rGO/MoSSe was immobilized on an FTO electrode, and molecularly imprinted polymers (MIPs) were prepared by electropolymerization on the rGO/MoSSe-modified FTO electrode with chlortetracycline as the template molecule and o-phenylenediamine as the functional monomer, so as to construct a molecularly imprinted photoelectrochemical (MIP-PEC) sensor. The determination of chlortetracycline was realized by the strategy of a "gate-controlled effect", and the detection range of the chlortetracycline concentration was 5.0 × 10-13-5 × 10-9 mol L-1 with a detection limit of 1.57 × 10-13 mol L-1. The sensor has been applied to the determination of chlortetracycline in animal-derived food samples.

Simple distance-based thread analytical device integrated with ion imprinted polymer for Zn2+ quantification in human urine samples.

This article presents the development of a distance-based thread analytical device (dTAD) integrated with an ion-imprinted polymer (IIP) for quantitative monitoring of zinc ions (Zn2+) in human urine samples. The IIP was easily chemically modified onto the thread channel using dithizone (DTZ) as a ligand to bind to Zn2+ with methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate (EGDMA) as well as 2,2-azobisisobutyronitrile (AIBN) as cross-linking agents to enhance the selectivity for Zn2+ detection. The imprinted polymer was characterized using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy and Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy (SEM-EDS). Under optimization, the linear detection range was from 1.0 to 20.0 mg L-1 (R2 = 0.9992) with a limit of detection (LOD) of 1.0 mg L-1. Other potentially interfering metal ions and molecules did not interfere with this approach, leading to high selectivity. Furthermore, our technique exhibits a remarkable recovery ranging from 100.48% to 103.16%, with the highest relative standard deviation (% RSD) of 5.44% for monitoring Zn2+ in human control urine samples, indicating high accuracy and precision. Similarly, there is no significant statistical difference between the results obtained using our method and standards on zinc supplement sample labels. The proposed method offers several advantages in detecting trace Zn2+ for point-of-care (POC) medical diagnostics and environmental sample analysis, such as ease of use, instrument-free readout, and cost efficiency. Overall, our developed dTAD-based IIP method holds potential for simple, affordable, and rapid detection of Zn2+ levels and can be applied to other metal ions' analysis.

Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

Molecularly imprinted polymer-coated silica microbeads for high-performance liquid chromatography.

Molecularly imprinted polymer (MIP)-based chromatographic separation materials, owing to their advantages of unique selectivity, low cost, suitable reproducibility, and acceptable stability, have attracted a great deal of research in different fields. In this investigation, a new type of MIP-coated silica (MIP/SiO2) separation material was developed using sulfamethoxazole as a template; the specific recognition ability of MIP and appropriate physicochemical properties (abundant Si-OH, suitable pore structure, good stability, etc.) of SiO2 microbeads were combined. The MIP/SiO2 separation materials were characterized carefully. Then, various compounds (such as sulfonamides, ginsenosides, nucleosides, and several pesticides) were used to comprehensively evaluate the chromatographic performances of the MIP/SiO2 column. Furthermore, the chromatographic performances of the MIP/SiO2 column were compared with those of other separation materials (such as non-imprinted polymer-coated silica, C18/SiO2, and bare silica) packed columns. The resolution value of all measured compounds was more than 1.51. The column efficiencies of 13 510 plates per meter (N m-1) for sulfamethoxazole, 11 600 N m-1 for ginsenoside Rd, and 10 510 N m-1 for 2'-deoxyadenosine were obtained. The acceptable results verified that the MIP/SiO2 column can be applied to separate highly polar drugs such as sulfonamides, ginsenosides, nucleosides, and pesticides.

Molecularly imprinted photopolymers combined with smartphone-based optical sensing for selective detection of bisphenol A in foods.

Bisphenol A (BPA), known for its endocrine-disrupting properties and potential to leach into food products, has led to significant food safety concerns. Therefore, the development of sensitive and selective BPA rapid detection methods is crucial. In this study, molecularly imprinted solid-phase extraction coupled to a colorimetric method was adopted for the smartphone-based determination of BPA. The molecularly imprinted polymer (MIP) was prepared via photopolymerization and used as a selective adsorbent material for SPE columns. The solid-phase extraction (SPE) columns with multiple cycles significantly reduced the extraction time to only 30 min. The developed method demonstrates useful sensitivity for BPA (LOD = 30 ppb). Furthermore, BPA migration from plastic packaging was evaluated under different storage conditions, revealing that microwave treatment for 5 min led to BPA release from polycarbonate packaging in juice and basic solutions. The MIP selective extraction/clean-up and smartphone-based optical sensor were successfully applied to BPA standard solutions and complex food samples (e.g., juice and tap water), resulting in reproducible and selective BPA determination (RSD ≤ 6%, n = 3). This rapid and cost-effective method of producing MIPs for BPA offers a promising solution for fast and low-cost sensing for on-site fresh food analysis.

Molecularly imprinted dispersive micro solid-phase extraction and tandem derivatization for the determination of histamine in fermented wines.

Histamine causes allergic reactions and can serve as an indicator for assessing food quality. This study designed and developed a dispersive micro solid-phase extraction (D-µSPE) method that combined the advantages of dispersive liquid-liquid extraction and solid-phase extraction (SPE). Molecularly imprinted polymers (MIPs) were employed as the solid phase in the D-µSPE method to extract histamine in wine samples. We used microwave energy to significantly reduce the synthesis time, achieving an 11.1-fold shorter synthesis time compared to the conventional MIP synthetic method. Under optimized D-µSPE conditions, our results showed that the dispersive solvent could effectively increase the adsorption performance of MIPs in wine samples by 97.7%. To improve the sensitivity of histamine detection in gas chromatography-mass spectrometry, we employed the microwave-assisted tandem derivatization method to reuse excess derivatization reagents and reduce energy consumption and reaction time. Calibration curves were constructed for wine samples spiked with 0-400 nmol histamine using the standard addition method, resulting in good linearity with a coefficient of determination of 0.999. The intra- and inter-batch relative standard deviations of the slope and intercept were < 0.7% and < 5.3%, respectively. The limits of quantitation and detection were 0.4 nmol and 0.1 nmol, respectively. The developed method was successfully applied to analyze the histamine concentration in 10 commercial wine samples. In addition, the AGREEprep tool was used to evaluate the greenness performance of the developed method, which obtained a higher score than the other reported methods.

Development of a molecularly imprinted polymer-based electrochemical sensor for the selective detection of nerve agent VX metabolite ethyl methylphosphonic acid in human plasma and urine samples.

This study focuses on the detection of ethyl methyl phosphonic acid (EMPA), a metabolite of the banned organophosphorus nerve agent VX. We developed an electrochemical sensor utilizing the molecularly imprinted polymer (MIP) based on 4-aminobenzoic acid (4-ABA) and tetraethyl orthosilicate for the selective detection of EMPA in human plasma and urine samples. The 4-ABA@EMPA/MIP/GCE sensor was constructed by a thermal polymerization process on a glassy carbon electrode and sensor characterization was performed by cyclic voltammetry and electrochemical impedance spectroscopy. The 4-ABA@EMPA/MIP/GCE sensor demonstrated impressive linear ranges 1.0 × 10-10 M-2.5 × 10-9 M for the standard solution, 1.0 × 10-10 M-2.5 × 10-9 M for the urine sample, and 1.0 × 10-10 M-1 × 10-9 M of EMPA for the plasma sample with outstanding detection limits of 2.75 × 10-11 M (standard solution), 2.11 × 10-11 M (urine), and 2.36 × 10-11 M (plasma). The sensor exhibited excellent recovery percentages ranging from 99.86 to 101.30% in urine samples and 100.62 to 101.08% in plasma samples. These findings underscore the effectiveness of the 4-ABA@EMPA/MIP/GCE as a straightforward, highly sensitive, and selective interface capable of detecting the target analyte EMPA in human plasma and urine samples.

Novel dummy molecularly imprinted polymer for simultaneous solid-phase extraction of stanozolol metabolites from urine.

Stanozolol, a synthetic derivative of testosterone, is one of the common doping drugs among athletes and bodybuilders. It is metabolized to a large extent and metabolites are detected in urine for a longer duration than the parent compound. In this study, a novel dummy molecularly imprinted polymer (DMIP) is developed as a sorbent for solid-phase extraction of stanozolol metabolites from spiked human urine samples. The optimized DMIP is composed of stanozolol as the dummy template, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker in a ratio of 1:10:80. The extracted analytes were quantitively determined using a newly developed and validated ultrahigh-performance liquid chromatography tandem mass spectrometry method, where the limits of detection and quantitation were 0.91 and 1.81 ng mL-1, respectively, fulfilling the minimum required performance limit decided on by the World Anti-Doping Agency. The mean percentage extraction recoveries for 3'-hydroxystanozolol, 4ß-hydroxystanozolol, and 16ß-hydroxystanozolol are 97.80% ± 13.80, 83.16% ± 7.50, and 69.98% ± 2.02, respectively. As such, the developed DMISPE can serve as an efficient cost-effective tool for doping and regulatory agencies for simultaneous clean-up of the stanozolol metabolites prior to their quantification.

Revolutionizing medicine: Molecularly imprinted polymers as precision tools in cancer diagnosis and antibiotic detection.

Molecularly imprinted polymers (MIPs) are pivotal in medicine, mimicking biological receptors with enhanced specificity and affinity. Comprising templates, functional monomers, and cross-linkers, MIPs form stable three-dimensional polymer networks. Synthetic templates like glycan and aptamers improve efficiency, guiding the molecular imprinting process. Cross-linking determines MIPs' morphology and mechanical stability, with printable hydrogels offering biocompatibility and customizable properties, mimicking native extracellular matrix (ECM) microenvironments. Their versatility finds applications in tissue engineering, soft robotics, regenerative medicine, and wastewater treatment. In cancer research, MIPs excel in both detection and therapy. MIP-based detection systems exhibit superior sensitivity and selectivity for cancer biomarkers. They target nucleic acids, proteins, and exosomes, providing stability, sensitivity, and adaptability. In therapy, MIPs offer solutions to challenges like multidrug resistance, excelling in drug delivery, photodynamic therapy, photothermal therapy, and biological activity regulation. In microbiology, MIPs serve as adsorbents in solid-phase extraction (SPE), efficiently separating and enriching antibiotics during sample preparation. They contribute to bacterial identification, selectively capturing specific strains or species. MIPs aid in detecting antibiotic residues using fluorescent nanostructures and developing sensors for sulfadiazine detection in food samples. In summary, MIPs play a pivotal role in advancing medical technologies with enhanced sensitivity, selectivity, and versatility. Applications range from biomarker detection to innovative cancer therapies, making MIPs indispensable for the accurate determination and monitoring of diverse biological and environmental samples.

Chiral acidic molecularly imprinted polymer for enantio-separation of norepinephrine racemate.

We are looking into how well a copolymeric material made of poly (maleic acid-co-4-vinylpyridine) cross-linked with divinylbenzene can separate L-norepinephrine (L-NEP) from (±)-NEP. The initial step in this direction was the synthesis and subsequent analysis of L-NEP-maleimide chiral derivative. A 4-vinylpyridine/divinylbenzene combination was copolymerized with the resultant chiral maleimide. After heating the polymer materials in a high-alkaline environment to breakdown the connecting imide bonds, they were acidified in an HCl solution to eliminate the incorporated L-NEP species. Fourier transform infrared spectroscopy (FTIR) and a scanning electron microscope were used to examine the imprinted L-NEP-imprinted materials. The manufactured L-NEP-imprinted materials exhibited selectivity characteristics that were over 11 times greater for L-NEP than D-norepinephrine. The highest capacity observed in Langmuir adsorption studies was 170 mg/g at a pH of 7. After optical separation using a column technique, it was determined that the enantiomeric excess levels of D-norepinephrine and L-NEP in the first feeding and subsequent recovery solutions were 95% and 81%, respectively.

Design and synthesis of nano-iron oxyhydroxide-based molecularly imprinted electrochemical sensors for trace-level carbendazim detection in actual samples.

Carbendazim (CBD) is widely used as a fungicide that acts as a pesticide in farming to prevent crop diseases. However, CBD can remain on crops for a long time. When consumed by humans and animals, it produces a range of toxic symptoms and poses a serious threat to their health. Therefore, the detection of CBD is necessary. Traditional assay strategies for CBD detection, although sensitive and practical, can hardly achieve fast, robust monitoring during food processing and daily life. Here, we designed a novel electrochemical sensor for CBD detection. In this method, iron oxyhydroxide nanomaterial (ß-FeOOH) was first prepared by hydrothermal method. Then, a molecularly imprinted polymer (MIP) layer was electropolymerized on the surface using CBD as the template and resorcinol (RC) as the functional monomer. The synergistic interaction between ß-FeOOH and MIP endows the MIP/ß-FeOOH/CC-based electrochemical sensor with high specificity and sensitivity. Under optimal conditions, the MIP/ß-FeOOH/CC-based sensor showed a wide linear range of 39 pM-80 nM for CBD and a detection limit as low as 25 pM. Therefore, the as-prepared sensor can be a practical and effective tool for pesticide residue detection.

Molecularly Imprinted Drug Carrier for Lamotrigine-Design, Synthesis, and Characterization of Physicochemical Parameters.

This study presents the initial attempt at introducing a magnetic molecularly imprinted polymer (MIP) designed specifically for lamotrigine with the purpose of functioning as a drug carrier. First, the composition of the magnetic polymer underwent optimization based on bulk polymer adsorption studies and theoretical analyses. The magnetic MIP was synthesized from itaconic acid and ethylene glycol dimethacrylate exhibiting a drug loading capacity of 3.4 ± 0.9 µg g-1. Structural characterization was performed using powder X-ray diffraction analysis, vibrating sample magnetometry, and Fourier transform infrared spectroscopy. The resulting MIP demonstrated controlled drug released characteristics without a burst effect in the phospahe buffer saline at pH 5 and 8. These findings hold promise for the potential nasal administration of lamotrigine in future applications.

Unlocking New Avenues: Solid-State Synthesis of Molecularly Imprinted Polymers.

Molecularly imprinted polymers (MIPs) are established artificial molecular recognition platforms with tailored selectivity towards a target molecule, whose synthesis and functionality are highly influenced by the nature of the solvent employed in their synthesis. Steps towards the "greenification" of molecular imprinting technology (MIT) has already been initiated by the elaboration of green MIT principles; developing MIPs in a solvent-free environment may not only offer an eco-friendly alternative, but could also significantly influence the affinity and expected selectivity of the resulting binding sites. In the current study the first solvent-free mechanochemical synthesis of MIPs via liquid-assisted grinding (LAG) is reported. The successful synthesis of the imprinted polymer was functionally demonstrated by measuring its template rebinding capacity and the selectivity of the molecular recognition process in comparison with the ones obtained by the conventional, non-covalent molecular imprinting process in liquid media. The results demonstrated similar binding capacities towards the template molecule and superior chemoselectivity compared to the solution-based MIP synthesis method. The adoption of green chemistry principles with all their inherent advantages in the synthesis of MIPs may not only be able to alleviate the potential environmental and health concerns associated with their analytical (e.g., selective adsorbents) and biomedical (e.g., drug carriers or reservoirs) applications, but might also offer a conceptual change in molecular imprinting technology.

Synthesis of Boronate Affinity-Based Oriented Dummy Template-Imprinted Magnetic Nanomaterials for Rapid and Efficient Solid-Phase Extraction of Ellagic Acid from Food.

Ellagic acid (EA) is a natural polyphenol and possesses excellent in vivo bioactivity and antioxidant behaviors, which play an important role in the treatment of oxidative stress-related diseases, such as cancer. Additionally, EA is also known as a skin-whitening ingredient. The content of EA would determine its efficacy. Therefore, the accurate analysis of EA content can provide more information for the scientific consumption of EA-rich foods and cosmetics. Nevertheless, the analysis of EA in these samples is challenging due to the low concentration level and the presence of interfering components with high abundance. Molecularly imprinted polymers are highly efficient pretreatment materials in achieving specific recognition of target molecules. However, the traditional template molecule (EA) could not be absolutely removed. Hence, template leakage continues to occur during the sample preparation process, leading to a lack of accuracy in the quantification of EA in actual samples, particularly for trace analytes. In addition, another drawback of EA as an imprinting template is that EA possesses poor solubility and a high price. Gallic acid (GA), called dummy templates, was employed for the synthesis of MIPs as a solution to these challenges. The approach used in this study was boronate affinity-based oriented surface imprinting. The prepared dummy-imprinted nanoparticles exhibited several significant advantages, such as good specificity, high binding affinity ((4.89 ± 0.46) × 10-5 M), high binding capacity (6.56 ± 0.35 mg/g), fast kinetics (6 min), and low binding pH (pH 5.0) toward EA. The reproducibility of the dummy-imprinted nanoparticles was satisfactory. The dummy-imprinted nanoparticles could still be reused even after six adsorption-desorption cycles. In addition, the recoveries of the proposed method for EA at three spiked levels of analysis in strawberry and pineapple were 91.0-106.8% and 93.8-104.0%, respectively, which indicated the successful application to real samples.

Molecularly Imprinted Polymers as Synthetic Antibodies for Protein Recognition: The Next Generation.

Molecularly imprinted polymers (MIPs) are chemical antibody mimics obtained by nanomoulding the 3D shape and chemical functionalities of a desired target in a synthetic polymer. Consequently, they possess exquisite molecular recognition cavities for binding the target molecule, often with specificity and affinity similar to those of antigen-antibody interactions. Research on MIPs targeting proteins began in the mid-90s, and this review will evaluate the progress made till now, starting from their synthesis in a monolith bulk format through surface imprinting to biocompatible soluble nanogels prepared by solid-phase synthesis. MIPs in the latter format will be discussed more in detail because of their tremendous potential of replacing antibodies in the biomedical domain like in diagnostics and therapeutics, where the workforce of antibodies is concentrated. Emphasis is also put on the development of epitope imprinting, which consists of imprinting a short surface-exposed fragment of a protein, resulting in MIPs capable of selectively recognizing the whole macromolecule, amidst others in complex biological media, on cells or tissues. Thus selecting the 'best' peptide antigen is crucial and in this context a rational approach, inspired from that used to predict peptide immunogens for peptide antibodies, is described for its unambiguous identification.

Improved selectivity of molecularly imprinted polymers based on the synergistic action of hydrogen bond and electrostatic interaction.

Based on the synergistic action of hydrogen bond and electrostatic interaction, provided by methacrylic acid and 2-aminoethyl ester hydrochloride (FM2), respectively, novel molecularly imprinted polymers (SA-MIPs) were designed to improve its selective recognition ability. Diclofenac sodium (DFC) was chosen as the template molecule of this study. The interaction and their recognition sites between two functional monomers and templates were confirmed by nuclear magnetic resonance hydrogen spectroscopy. Because of the synergistic action of hydrogen bond and electrostatic interaction, the imprinting factor (IF) of SA-MIPs (IF = 2.26) is superior to the corresponding monofunctional monomer imprinting materials (IF = 1.52, 1.20) and the materials using two functional monomers with an only single type of interaction (IF = 1.54, 1.75). The results of selective adsorption experiments indicate that the selective recognition ability of SA-MIPs is significantly better than that of the other four MIPs, and the difference in selectivity coefficient for methyl orange is the largest between SA-MIPs and the MIPs only using FM2, which is about 70 times. In addition, x-ray photoelectron spectroscopy was used to verify the interaction between SA-MIPs and the template. This work and its explanation of the interaction mechanism at the molecular level will be helpful for the rational design of novel MIPs with higher selectivity. Besides, SA-MIPs have good adsorption performance (37.75 mg/g) for DFC in aqueous solutions, which could be used as potential adsorption materials for the effective removal of DFC in the aquatic environment.

A novel molecularly imprinted electrochemical sensor for the ultrasensitive detection of tert-butylhydroquinone in edible oils.

Tert-butylhydroquinone (TBHQ) is widely used to increase the stability of food products; however, it is considered to be a highly unsafe preservative ingredient that has caused serious damage to human health. Thus, in this paper, a novel molecularly imprinted electrochemical sensor was designed for ultrasensitive, and selective detection of TBHQ in edible oils. The sensor was based on the molecularly imprinted polymer (MIP) synthesized with multiwalled carbon nanotube (MWCNT), and gold nanoparticle (GNP), as the coating materials, o-phenylenediamine (o-PDA) as the functional monomer, and TBHQ as the template molecule. The electrochemical behavior of MIP/GNP/MWCNT/GCE was studied using several electrochemical methods, which showed a low detection limit of 5 nM. Furthermore the sensor demostrated excellent stability, selectivity, repeatability, and reproducibility. It was successfully used to detect TBHQ in edible oils, with recoveries ranging from 98.44% to 102.09% and relative standard deviations (RSDs) of less than 2.16%, indicating that TBHQ detection in actual samples is both possible and accurate.

Mycotoxins detection: view in the lens of molecularly imprinted polymer and nanoparticles.

Molecularly imprinted polymers (MIPs) are tailor-made functional composites which selectively recognize and bind the target molecule of interest. MIP composites are products of the massively cross-linked polymer matrices, generated via polymerization, with bio-inspired recognition cavities that are morphologically similar in size, shape and spatial patterns to the target conformation. These features have enabled researchers to expand the field of molecular recognition, more specifically for target with peculiar requirements. Nevertheless, MIPs alone are characterized with weak sensitivity. Besides, nanoparticles (NPs) are remarkably sensitive but also suffer from poor selectivity. Intriguingly, the combination of the two results in a highly sensitive and selective MIP composite. For instance, the conjugation of different functional NPs with MIPs can generate new flexible target capture tools, either a dynamic sensor or a novel drug delivery system. In this regard, although the technology is considered an established and feasible approach, it is still perceived as a burgeoning technology for various fields, which makes it unceasingly worthy reviewing. Therefore, in this review, we attempt to give an update on various custom-made biosensors based on MIPs in combination with various NPs for the detection of mycotoxins, the toxic secondary metabolites of fungi. We first summarize the classification, prevalence, and toxicological characteristics of common mycotoxins. Next, we provide an overview of MIP composites and their characterization, and then segment the role of NPs with respect to common types of MIP-based sensors. At last, conclusions and outlook are discussed.

Sensitive detection of synthetic cannabinoids in human blood using magnetic polydopamine molecularly imprinted polymer nanocomposites.

Synthetic cannabinoids (SCs) are a series of artificial chemical substances with pharmacological properties similar to those of natural cannabinoids and their abuse poses a great risk to social security and human health. However, the highly sensitive detection of low concentrations of SCs in human serum remains a great challenge. In this work, we developed a highly sensitive, rapid and highly selective method for the detection of SCs in human serum. Magnetic molecularly imprinted polymer (MIP) nanocomposites were prepared through self-polymerization of dopamine and template molecules on the surfaces of magnetic beads. 9H-Carbazole-9-hexanol (9CH) was used as a template molecule because of its long chain structure shared with six synthetic cannabinoids and its ability to provide specific recognition sites. With these magnetic MIP nanoparticles, six SCs could be rapidly and effectively extracted from human blood. The concentrations of six SCs could be accurately determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. The limits of detection were in the range of 0.1-0.3 ng mL-1. The proposed method is characterized by high sensitivity and selectivity, and has great potential for application in the analysis of practical samples.