Dual modules-molecularly imprinted patch-enabled enantioselectively controlled release of racemic drugs for transdermal delivery.

Over 90 % of chiral drugs applied in transdermal drug delivery system (TDDS) are racemates, significantly increasing risks of side effects. Herein, we designed a chiral molecularly imprinted patch (CMIP) that achieved enantioselectively controlled release of S-enantiomers (eutomers) and inhibited the release of R-enantiomers (distomers) for transdermal drug delivery. It is composed of chiral pressure sensitive adhesive (PSA) and molecularly imprinted polymers (MIP), showing better transdermal delivery of S-enantiomers than that of R-enantiomers in vitro (1.86-fold) and in vivo (3.74-fold), significantly decreasing the intake of distomers. Additionally, synthesized fluorescent probe enantiomers visualized enantioselective process of CMIP. Furthermore, investigations of molecular mechanism indicated that dependence on spatial conformation was dominant. On one hand, imprinted cavity of MIP with D-isomer and stronger chiral interaction with R-enantiomers led to more specific adsorption. On the other hand, L-isomer of PSA controlled the release of S-enantiomers by multiple interaction including chiral H-bond, π-π interaction and Van der Waals force. Tthus, the innovatively designed transdermal patch with enantioselective ability released eutomers of racemate and simultaneously inhibited release of distomers, significantly improving therapeutical efficiency and avoiding overdose.

Sensitive Coatings Based on Molecular-Imprinted Polymers for Triazine Pesticides' Detection.

Triazine pesticide (atrazine and its derivatives) detection sensors have been developed to thoroughly check for the presence of these chemicals and ultimately prevent their exposure to humans. Sensitive coatings were designed by utilizing molecular imprinting technology, which aims to create artificial receptors for the detection of chlorotriazine pesticides with gravimetric transducers. Initially, imprinted polymers were developed, using acrylate and methacrylate monomers containing hydrophilic and hydrophobic side chains, specifically for atrazine, which shares a basic heterocyclic triazine structure with its structural analogs. By adjusting the ratio of the acid to the cross-linker and introducing acrylate ester as a copolymer, optimal non-covalent interactions were achieved with the hydrophobic core of triazine molecules and their amino groups. A maximum sensor response of 546 Hz (frequency shift/layer height equal to 87.36) was observed for a sensitive coating composed of 46% methacrylic acid and 54% ethylene glycol dimethacrylate, with a demonstrated layer height of 250 nm (6.25 kHz). The molecularly imprinted copolymer demonstrated fully reversible sensor responses, not only for atrazine but also for its metabolites, like des-ethyl atrazine, and structural analogs, such as propazine and terbuthylazine. The efficiency of modified molecularly imprinted polymers for targeted analytes was tested by combining them with a universally applicable quartz crystal microbalance transducer. The stable selectivity pattern of the developed sensor provides an excellent basis for a pattern recognition procedure.

Fabrication and properties of temperature-responsive imprinted sensors based on fluorescently labeled yeast cells via MVL ATRP.

Temperature-responsive yeast cell-imprinted sensors (CIPs/AuNPs/Ti3C2Tx/AuNPs/Au) were prepared based on fluorescein isothiocyanate labeled yeast cells (FITC-yeast) via metal-free visible-light-induced atom transfer radical polymerization (MVL ATRP). Here, N-isopropyl acrylamide (NIPAM) was used as a temperature-responsive functional monomer, α-methacrylic acid (MAA) was chosen as an auxiliary functional monomer, N,N'-methylene bisacrylamide (MBA) was used as a cross-linker, and FITC-yeast was selected as both a template and photocatalyst. Under the optimal conditions, the detection range of the yeast cell-imprinted sensor toward yeast cells was 1.0 × 102 to 1.0 × 109 cells per mL, and the detection limit was 11 cells per mL (S/N = 3), with a linear equation of ΔI (µA) = 8.44 log[C (cells per mL)] + 7.62 (R2 = 0.993). The sensor showed good selective recognition in the presence of interfering substances such as autolyzed yeast cells (AY), dead yeast cells (DY), human mammary epithelial cells (MCF-10A), human breast cancer cells (MCF-7) and Escherichia coli (EC). The sensor also had good consistency and reproducibility. Finally, spiked recovery experiments were performed to investigate the recognition of yeast cells in the actual sample using the yeast cell-imprinted sensor. The spiked recoveries were all in the range of 98.5-108.0%, and the RSD values were all less than 4%, indicating that the sensor had good application prospects.

Gelatin-based carbon quantum dot-molecularly imprinted polymer: Safe photoluminescent core-shell nano-carrier for the pH-responsive anticancer drug delivery.

This study aims to synthesize a core-shell gelatin-based carbon quantum dot-molecularly imprinted polymer (MIP@g-CQD) via the precipitation free-radical polymerization process using methotrexate (MTX) as a model anticancer template. To investigate the efficiency of the prepared photoluminescent MIP@g-CQD as a pH-responsive nano-carrier, MTX was loaded into MIP@g-CQD by soaking in a drug solution and the release behavior of the loaded drug was evaluated in the necessary pH values (7.4, 5). The successful synthesis of materials was characterized using PL, TEM, FE-SEM, DLS, and FT-IR analyses. Interestingly, the created cavities in the core-shell nano-carriers can interact with the MTX molecules effectively, leading to an increase in the loading capacity. According to the obtained results from Langmuir adsorption isotherms, the imprinting factor was calculated (IF = 4.91). Also, the binding kinetics of MTX revealed the creation of particular recognition sites in the core-shell polymeric network. The MTX-loaded MIP@g-CQD displayed a low rate and limited release at the simulated physiological environment (pH 7.4, 37 °C), but it is increased at tumor tissue (pH 5, 41 °C) conditions, which can lead to long-term and sustained release of MTX in the desired target. This property of MIP@g-CQD could avoid the release of MTX in normal physiological conditions, decreasing the possible side effects of MTX drug. Owing to the existence of amide functional groups in the nano-carrier structure and its negatively charged nature, the MTT assay displayed desirable cytotoxicity against the breast cancer cell line (MCF-7) for the MTX-loaded nano-carrier. According to the obtained results, the prepared safe photoluminescent MIP@g-CQD with appropriate pH-responsivity has a high ability to be applied as an anticancer and bio-detection agent.

Site-Selective Functionalization of Molecularly Imprinted Nanoparticles to Recognize Lysine-Rich Peptides.

Sequence-selective binding of peptides has been a long-standing goal of chemists. As one of the most abundant amino acids in proteins, lysine plays an important role in protein functions as well as in antimicrobial and cell-penetrating peptides. Herein, we report molecularly imprinted nanoparticles (NPs) with high sequence selectivity for lysine-rich peptides. The NPs are prepared from molecular imprinting of cross-linkable surfactant micelles and postmodification of the imprinted pockets by photoaffinity labeling. The method allows carboxylic acids to be installed precisely near the lysine amino side chains, greatly enhancing the binding strengths of lysine-rich peptides. Small variations in the peptide sequence can be distinguished, and the binding affinity correlates positively with the number of lysine groups in model tripeptides. The method applies to complex lysine-rich biological peptides, achieving hundreds of nanomolar binding affinities and excellent binding specificities.

Engineering of dual recognition functional aptamer-molecularly imprinted polymeric solid-phase microextraction for detecting of 17ß-estradiol in meat samples.

In this study, an enhanced selective recognition strategy was employed to construct a novel solid-phase microextraction fiber coating for the detection of 17ß-estradiol, characterized by the combination of aptamer biorecognition and molecularly imprinted polymer recognition. Benefiting from the combination of molecularly imprinted and aptamer, aptamer-molecularly imprinted (Apt-MIP) fiber coating had synergistic recognition effect. The effects of pH, ion concentration, extraction time, desorption time and desorption solvent on the adsorption capacity of Apt-MIP were investigated. The adsorption of 17ß-estradiol on Apt-MIP followed pseudo-second order kinetic model, and the Freundlich isotherm. The process was exothermic and thermodynamically spontaneous. Compared with polymers that only rely on imprinted recognition, non-imprinted recognition or aptamer affinity, Apt-MIP had the best recognition performance, which was 1.30-2.20 times that of these three materials. Furthermore, the adsorption capacity of Apt-MIP for 17ß-estradiol was 885.36-1487.52 times than that of polyacrylate and polydimethylsiloxane/divinylbenzone commercial fiber coatings. Apt-MIP fiber coating had good stability and could be reused for more than 15 times. Apt-MIP solid-phase microextraction coupled with high-performance liquid chromatography was successfully applied to the determination of 17ß-estradiol in pork, chicken, fish and shrimp samples, with satisfactory recoveries of 79.61 %-105.70 % and low limits of detection (0.03 µg/kg). This work provides new perspectives and strategies for sample pretreatment techniques based on molecular imprinting technology and improves analytical performance.

Nanoparticles that Distinguish Chemical and Supramolecular Contexts of Lysine for Single-Site Functionalization of Protein.

Lysine is one of the most abundant residues on the surface of proteins and its site-selective functionalization is extremely challenging. The existing methods of functionalization rely on differential reactivities of lysine on a protein, making it impossible to label less reactive lysines selectively. We here report polymeric nanoparticles that mimic enzymes involved in the posttranslational modifications of proteins that distinguish the chemical and supramolecular contexts of a lysine and deliver the labeling reagent precisely to its ε amino group. The nanoparticles are prepared through molecular imprinting of cross-linkable surfactant micelles, plus an in situ, on-micelle derivatization of the peptide template prior to the imprinting. The procedures encode the polymeric nanoparticles with all the supramolecular information needed for sequence identification and precise labeling, allowing single-site functionalization of a predetermined lysine on the target protein in a mixture.

Molecular dynamics simulations in pre-polymerization mixtures for peptide recognition.

CONTEXT: Molecularly imprinted polymers (MIPs) have promising applications as synthetic antibodies for protein and peptide recognition. A critical aspect of MIP design is the selection of functional monomers and their adequate proportions to achieve materials with high recognition capacity toward their targets. To contribute to this goal, we calibrated a molecular dynamics protocol to reproduce the experimental trends in peptide recognition of 13 pre-polymerization mixtures reported in the literature for the peptide toxin melittin. METHODS: Three simulation conditions were tested for each mixture by changing the box size and the number of monomers and cross-linkers surrounding the template in a solvent-explicit environment. Fully atomistic MD simulations of 350 ns were conducted with the AMBER20 software, with ff19SB parameters for the peptide, gaff2 parameters for the monomers and cross-linkers, and the OPC water model. Template-monomer interaction energies under the LIE approach showed significant differences between high-affinity and low-affinity mixtures. Simulation systems containing 100 monomers plus cross-linkers in a cubic box of 90 Å3 successfully ranked the mixtures according to their experimental performance. Systems with higher monomer densities resulted in non-specific intermolecular contacts that could not account for the experimental trends in melittin recognition. The mixture with the best recognition capacity showed preferential binding to the 13-26-α-helix, suggesting a relevant role for this segment in melittin imprinting and recognition. Our findings provide insightful information to assist the computational design of molecularly imprinted materials with a validated protocol that can be easily extended to other templates.

Surface modification of PVDF ultrafiltration membranes using spacer arms and synthetic receptors for virus capturing and separation.

Although membrane technology has demonstrated outstanding pathogen removal capabilities, current commercial membranes are insufficient for removing small viruses at trace levels due to certain limitations. The theoretical and practical significance of developing a new form of hydrophilic, anti-fouling, and virus-specific ultra-purification membrane with high capturing and separation efficiency, stability, and throughput for water treatment is of the utmost importance. In this study, molecularly imprinted membranes (MIMs) were fabricated from polyvinylidene fluoride (PVDF) membranes utilizing novel surface hydrophilic modification techniques, followed by the immobilization of virus-specific molecularly imprinted nanoparticles (nanoMIPs) as synthetic receptors. Three distinct membrane functionalization strategies were established and optimized for the first time: membrane functionalization with (i) polyethyleneimine (PEI) and dopamine (DOP), (ii) PEI and 3-(chloropropyl)-trimethoxysilane (CTS), and (iii) chitosan (CS). Hydrophilicity was enhanced significantly as a result of these modification strategies. Additionally, the modifications enabled spacer arms between the membrane surface and the nanoMIPs to decrease steric hindrance. The surface chemistry, morphology, and membrane performance results from the characterization analysis of the MIMs demonstrated excellent hydrophilicity (e.g., the functionalized membrane presented 37.84° while the unmodified bare membrane exhibited 128.94° of water contact angle), higher permeation flux (145.96 L m-2 h-1 for the functionalized membrane), excellent uptake capacity (up to 99.99 % for PEI-DOP-MIM and CS-MIM), and recovery (more than 80 % for PEI-DOP-MIM). As proof of concept, the cutting-edge MIMs were able to eliminate the model adenoviruses up to 99.99 % from water. The findings indicate that the novel functionalized PVDF membranes hold promise for implementation in practical applications for virus capture and separation.

Double Imprinted Nanoparticles for Sequential Membrane-to-Nuclear Drug Delivery.

Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life-threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost-effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor-mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof-of-concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three-dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.

Functionalized nano cellulose double-template imprinted aerogel microsphere for the targeted enrichment of taxanes.

Paclitaxel, a diterpenoid isolated from the bark of Taxus wallichiana var. chinensis (Pilger) Florin, is currently showing significant therapeutic effects against a variety of cancers. Baccatin III (Bac) and 10-Deacetylbaccatin III (10-DAB) are in great demand as important precursors for the synthesis of paclitaxel. This work aims to develop a simple, rapid and highly selective, safe, and non-polluting molecularly imprinted material for 10-DAB and Bac enrichment. In this study, we innovatively prepared molecularly imprinted materials with nanocellulose aerogel microspheres and 2-vinylpyridine (2-VP) as a bifunctional monomer, and 10-DAB and Bac as bis-template molecules. In particular, functionalized nanocellulose dual-template molecularly imprinted aerogel microsphere (FNCAG-DMIM) were successfully synthesized by the bifunctional introduction of functional nanocellulose aerogel microsphere (FNCAG) modified with Polyethyleneimine (PEI) as a carrier and functional monomer, which provided a large number of recognition sites for bimodal molecules. FNCAG-DMIM showed high specificity for 10-DAB and Bac specific assays. Under the optimal experimental conditions, the adsorption capacities of FNCAG-DMIM for 10-DAB and Bac reached 52.27 mg g-1 and 53.81 mg g-1, respectively. In addition, it showed good reliability and practicality in the determination of real samples. The present study extends the research on the synthesis of natural functional monomers by molecularly imprinted materials and opens up new horizons for the targeted isolation of plant compounds by dual-template molecularly imprinted materials.

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.

Chitosan-graphene quantum dot-based molecular imprinted polymer for oxaliplatin release.

Molecularly imprinted polymers (MIPs) have garnered the interest of researchers in the drug delivery due to their advantages, such as exceptional durability, stability, and selectivity. In this study, a biocompatible MIP drug adsorption and delivery system with high loading capacity and controlled release, was prepared based on chitosan (CS) and graphene quantum dots (GQDs) as the matrix, and the anticancer drug oxaliplatin (OXAL) as the template. Additionally, samples without the drug (non-imprinted polymers, NIPs) were created for comparison. GQDs were produced using the hydrothermal method, and samples underwent characterization through FTIR, XRD, FESEM, and TGA. Various experiments were conducted to determine the optimal pH for drug adsorption, along with kinetic and isotherm studies, selectivity assessments, in vitro drug release and kinetic evaluations. The highest drug binding capacity was observed at pH 6.5. The results indicated the Lagergren-first-order kinetic model (with rate constant of 0.038 min-1) and the Langmuir isotherm (with maximum adsorption capacity of 17.15 mg g-1) exhibited better alignment with the experimental data. The developed MIPs displayed significant selectivity towards OXAL, by an imprinting factor of 2.88, in comparison to two similar drugs (cisplatin and carboplatin). Furthermore, the analysis of the drug release profile showed a burst release for CS-Drug (87% within 3 h) at pH 7.4, where the release from the CS-GQD-Drug did not occur at pH 7.4 and 10; instead, the release was observed at pH 1.2 in a controlled manner (100% within 28 h). Consequently, this specific OXAL adsorption and delivery system holds promise for cancer treatment.

Surface-enhanced Raman sensor with molecularly imprinted nanoparticles as highly sensitive recognition material for cancer marker amino acids.

Surface-enhanced Raman scattering (SERS) is a powerful technique primarily due to its high sensitivity and signal-enhancing properties, which enable the identification of unique vibrational fingerprints. These fingerprints can be used for the diagnosis and monitoring of diseases such as cancer. It is crucial to selectively identify cancer biomarkers for early diagnosis. A correlation has been established between the reduction in the concentration of specific amino acids and the stage of the disease, particularly tryptophan (TPP) and tyrosine (TRS) in individuals diagnosed with prostate cancer. In this work, we present a strategy to analyze TPP and TRS amino acids using molecularly imprinted polymer nanoparticles (nanoMIPs), which selectively detect target molecules in a SERS sensor. NanoMIPs are synthesized using the solid-phase molecular imprinting method with TPP and TRS as templates. These are then immobilized on a SERS substrate with gold nanoparticles to measure samples prepared from tryptophan and tyrosine in phosphate-buffered saline. The detection and quantification limits of the designed sensor are 7.13 µM and 23.75 µM for TPP, and 22.11 µM and 73.72 µM for TRS, respectively. Our study lays the groundwork for future investigations utilizing nanoMIPs in SERS assessments of TPP and TRS as potential biomarkers for prostate cancer detection.

Preparation and optimization of dummy molecularly imprinted polymer-based solid-phase extraction system for selective enrichment of p-toluene sulfonate esters genotoxic impurities.

Sulfonate esters, one class of genotoxic impurities (GTIs), have gained significant attention in recent years due to their potential to cause genetic mutations and cancer. In the current study, we employed the dummy template molecular imprinting technology with a dummy template molecule replacing the target molecule to establish a pretreatment method for samples containing p-toluene sulfonate esters. Through computer simulation and ultraviolet-visible spectroscopy analysis, the optimal functional monomer acrylamide and polymerization solvent chloroform were selected. Subsequently, a dummy template molecularly imprinted polymer (DMIP) was prepared by the precipitation polymerization method, and the polymer was characterized in morphology, particle size, and composition. The results of the adsorption and enrichment study demonstrated that the DMIP has high adsorption capability (Q = 7.88 mg/g) and favorable imprinting effects (IF = 1.37); Further, it could simultaneously adsorb three p-toluene sulfonate esters. The optimal adsorption conditions were obtained by conditional optimization of solid-phase extraction (SPE). A pH 7 solution was selected as the loading condition, the methanol/1 % phosphoric acid solution (20:80, v/v) was selected as the washing solution, and acetonitrile containing 10 % acetic acid in 6 mL was selected as the elution solvent. Finally, we determined methyl p-toluene sulfonate alkyl esters, ethyl p-toluene sulfonate alkyl esters, and isopropyl p-toluene sulfonate alkyl esters in tosufloxacin toluene sulfonate and capecitabine at the 10 ppm level (relative to 1 mg/mL active pharmaceutical ingredient (API) samples) by using DMIP-based SPE coupled with HPLC. This approach facilitated the selective enrichment of p-toluene sulfonate esters GTIs from complex API samples.

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.

Precise Capture and Dynamic Release of Circulating Liver Cancer Cells with Dual-Histidine-Based Cell Imprinted Hydrogels.

Circulating tumor cells (CTCs) detection presents significant advantages in diagnosing liver cancer due to its noninvasiveness, real-time monitoring, and dynamic tracking. However, the clinical application of CTCs-based diagnosis is largely limited by the challenges of capturing low-abundance CTCs within a complex blood environment while ensuring them alive. Here, an ultrastrong ligand, l-histidine-l-histidine (HH), specifically targeting sialylated glycans on the surface of CTCs, is designed. Furthermore, HH is integrated into a cell-imprinted polymer, constructing a hydrogel with precise CTCs imprinting, high elasticity, satisfactory blood compatibility, and robust anti-interference capacities. These features endow the hydrogel with excellent capture efficiency (>95%) for CTCs in peripheral blood, as well as the ability to release CTCs controllably and alive. Clinical tests substantiate the accurate differentiation between liver cancer, cirrhosis, and healthy groups using this method. The remarkable diagnostic accuracy (94%), lossless release of CTCs, material reversibility, and cost-effectiveness ($6.68 per sample) make the HH-based hydrogel a potentially revolutionary technology for liver cancer diagnosis and single-cell analysis.

SERS biosensor with plastic antibodies for detection of a cancer biomarker protein.

Surface-enhanced Raman scattering (SERS) is a powerful method for detecting breast cancer-specific biomarkers due to its extraordinary enhancement effects obtained by localized surface plasmon resonance (LSPR) in metallic nanostructures at hotspots. In this research, gold nanostars (AuNSs) were used as SERS probes to detect a cancer biomarker at very low concentrations. To this end, we combined molecularly imprinted polymers (MIPs) as a detection layer with SERS for the detection of the biomarker CA 15-3 in point-of-care (PoC) analysis. This required two main steps: (i) the deposition of MIPs on a gold electrode, followed by a second step (ii) antibody binding with AuNSs containing a suitable Raman reporter to enhance Raman signaling (SERS). The MPan sensor was prepared by electropolymerization of the monomer aniline in the presence of CA 15-3. The template molecule was then extracted from the polymer using sodium dodecyl sulfate (SDS). In parallel, a control material was prepared in the absence of the protein (NPan). Surface modification for the control was performed using electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The performance of the sensor was evaluated using the SERS technique, in which the MPan sensor is first incubated with the protein and then exposed to the SERS probe. Under optimized conditions, the device showed a linear response to CA 15-3 concentrations from 0.016 to 248.51 U mL-1 in a PBS buffer at pH 7.4 in 1000-fold diluted serum. Overall, this approach demonstrates the potential of SERS as an optical reader and opens a new avenue for biosensing applications.

In situ detection of dopamine in single living cells by molecularly imprinted polymer-functionalized nanoelectrodes.

In situ detection of dopamine (DA) at single-cell level is critical for exploring neurotransmitter-related biological processes and diseases. However, the low content of DA and a variety of distractors with similar oxidation potentials as DA in cells brought great challenges. Here, a sensitive and specific electrochemical nanosensor was proposed for in situ detection of DA in single living cells based on nanodiamond (ND) and molecularly imprinted polymer (MIP)-functionalized carbon fiber nanoelectrode (ND/MIP/CFNE). Due to its excellent electrocatalytic property, ND was modified to the surface of CFNE based on amide bonding. Compared with bare CFNE, ND-modified CFNE can enhance oxidation currents of DA by about 4-fold, improving signal-to-noise ratio and detection sensitivity. MIP was further electropolymerized on the surface of nanoelectrodes to achieve specific capture and recognition of DA, which could avoid the interference of complex matrix and analogs in cells. Taking advantage of the precise positioning capability of a single-cell analyzer and micromanipulator, ND/MIP/CFNE could be precisely inserted into different locations of single cells and monitor oxidation signal of DA. The concentration of DA in the cytoplasm of single pheochromocytoma (PC12) cell was measured to be about 0.4 µM, providing a sensitive and powerful method for single-cell detection. Furthermore, the nanoelectrodes can monitor the fluctuation of intracellular DA under drug stimulation, providing new ideas and methods for new drug development and efficacy evaluation.

Tailor-made molecular imprints for biological event intervention.

Molecular imprints, which are crosslinked architectures containing specific molecular recognition cavities for targeting compounds, have recently transitioned from in vitro diagnosis to in vivo treatment. In current application scenarios, it has become an important topic to create new biomolecular recognition pathways through molecular imprinting, thereby inhibiting the pathogenesis and regulating the development of diseases. This review starts with a pathological analysis, mainly focusing on the corresponding artificial enzymes, enzyme inhibitors and antibody mimics with enhanced functions that are created by molecular imprinting strategies. Recent advances are highlighted in the use of molecular imprints as tailor-made nanomedicines for the prevention of three major diseases: metabolic syndrome, cancer, and bacterial/viral infections.