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    Chinese Journal of Chromatography
    2026, Vol. 44, No. 2
    Online: 08 February 2026

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    Reviews
    Molecularly imprinted polymers: novel green preparation methods and cutting-edge applications review
    LI Fei, JIA Baolin, HU Qiao, HE Xiwen, CHEN Langxing, ZHANG Yukui
    2026, 44 (2):  119-133.  DOI: 10.3724/SP.J.1123.2025.06010
    Abstract ( 56 )   HTML ( 6 )   PDF (1329KB) ( 22 )  

    Molecular imprinting technology is an emerging technique that achieves specific recognition of imprinted molecules by simulating the interactions between antibody and antigen or between enzyme and substrate. The core of this technology lies in the preparation of molecularly imprinted polymers (MIPs). However, traditional preparation methods of MIPs face severe challenges due to drawbacks such as uneven morphology, limited conformational choices for molecular recognition, random and uncontrollable polymerization, and environmental safety hazards, making the innovation of synthesis methods urgent. In recent years, with the proposal of green chemistry concepts and the development of green synthesis methods, the preparation technology of MIPs has gradually transitioned towards resource-saving and environment-friendly directions. The preparation of green molecularly imprinted polymers (GMIPs) aims to replace traditional methods by reducing the use of solvents and the generation of waste liquids during the synthesis process, employing safe and non-toxic reagents and solvents, and developing efficient synthesis methods to improve energy efficiency. Green solvents such as water, supercritical carbon dioxide, deep eutectic solvents, and ionic liquids are used to replace organic solvents in the synthesis of traditional MIPs. Functional monomers with biocompatibility and environmental friendliness, including chitosan, cellulose, itaconic acid, dopamine, and cyclodextrin, have found increasing applications in the preparation of MIPs. In addition, the preparation technology of MIPs is gradually transitioning towards resource conservation and environmental friendliness. The development of novel synthesis methods such as green precipitation polymerization, microwave-assisted synthesis, supercritical fluid technology, ultrasound-assisted polymerization, and computer simulation-assisted design and characterization has promoted the popularity of GMIPs preparation methods. These novel preparation methods significantly improve the functionality and environmental compatibility of MIPs by precisely regulating reaction conditions, reducing energy consumption, and minimizing harmful by-products. They not only optimize the synthesis efficiency of MIPs, but also provide new ideas for solving the bottlenecks of traditional methods in morphology control and large-scale production. GMIPs, with their high selectivity, stability, and tunability, have shown breakthrough applications in multiple frontier fields. For example, in environmental monitoring, GMIPs are applied to detect heavy metal ions (such as lead and arsenic), organic pollutants (such as pesticides and antibiotics), and explosives in aqueous environments. In the field of food safety analysis, GMIPs enable efficient enrichment and detection of trace pollutants (such as pesticide residues, veterinary drugs, and mycotoxins) in food matrices, significantly outperforming traditional methods. In biomedical applications, GMIPs are developed as drug controlled-release systems, biomarker detection platforms, and targeted therapeutic carriers. In addition, the efficient performance of GMIPs in sample pretreatment (such as solid-phase extraction) further reduces analysis costs and reduces reliance on organic solvents. This paper reviews the novel preparation methods of GMIPs and their applications in environmental monitoring, food safety, and biomedicine in recent years, and provides an outlook on the development of GMIPs.

    Design and synthesis of molecularly imprinted polymers and their applications in medical diagnosis and biocatalysis
    SONG Qingmei, LI Xinhao, LYU Yongqin
    2026, 44 (2):  134-150.  DOI: 10.3724/SP.J.1123.2025.06013
    Abstract ( 37 )   HTML ( 6 )   PDF (2209KB) ( 22 )  

    Molecularly imprinted technology (MIT) represents an advanced synthetic strategy that emulates biological recognition mechanisms, such as antigen-antibody or enzyme-substrate interactions, by creating three-dimensional cavity-like structures through the directional assembly of functional monomers around a template molecule. This process generates spatial and functional complementarity, enabling highly selective recognition of target species. Molecularly imprinted polymers (MIPs), often described as “synthetic antibodies”, overcome the intrinsic limitations of natural biomolecules by offering superior selectivity, robustness, cost-effectiveness, and structural tunability. These features position MIPs as promising alternatives to natural antibodies in targeted sensing and drug delivery, with broad applications across biomedical, environmental, and pharmaceutical domains, including pollutant detection, and food safety monitoring. Despite substantial progress, key challenges remain, such as uneven imprinting layers, template residue, and limited aqueous compatibility in macromolecular imprinting. Furthermore, issues of industrial scalability, unclear recognition mechanisms, and insufficient integration with emerging fields such as microfluidics and artificial intelligence have hindered large-scale translation. In recent years, our research team has systematically advanced MIT through a tri-dimensional strategy encompassing high-throughput monomer screening, mechanistic elucidation of molecular recognition, and directional assembly of functional units. By establishing a standardized monomer library and integrating molecular dynamics simulations, we achieved precise material design under complex conditions. Through process optimization and material innovation, we developed a highly efficient solid-phase surface imprinting method that enables the fabrication of smart MIPs with stimuli-responsive properties (e.g., temperature and pH). These MIPs exhibit markedly enhanced binding affinity, with equilibrium dissociation constant (KD) reaching 10-12 mol/L, over four orders of magnitude higher than those of non-imprinted polymers (NIPs). Building on these advances, we established cross-disciplinary application platforms, including affinity-based protein separation and purification systems capable of efficient dual-enzyme cascade immobilization and inactivated enzyme renaturation. In the biomedical domain, we developed ultrasensitive biosensing methods achieving picogram-level detection of heart failure biomarkers and single-digit (≈5 cells/mL) detection of cancer cells in whole blood, extending these methods toward integrated tumor theranostics and microbial community regulation. This paper comprehensively summarizes our team’s recent innovations in the rational design, functionalized fabrication, and cross-disciplinary applications of MIPs, spanning biosensing, biocatalysis, and biomedical diagnostics/therapeutics, while contextualizing these within the latest global advances in biomedicine and catalysis. Looking forward, we identify three strategic research frontiers for next-generation MIT. (i) Smart responsive material systems: design MIPs capable of multi-stimuli responsiveness (e.g., magnetic, photothermal, and pH cues) to enable programmable drug release, real-time signal monitoring, and dynamic feedback regulation. (ii) Quantitative modeling of dynamic recognition: establish multi-scale theoretical frameworks to elucidate coupling between cavity flexibility and target conformational dynamics, guiding structure optimization and function-oriented design of adaptive MIPs. (iii) Integrated intelligent theranostic platforms: integrate microfluidics and biomimetic recognition modules into closed-loop systems capable of biomarker detection, targeted delivery, and real-time therapeutic feedback, bridging the gap between in vitro sensing and in vivo precision intervention. Synergistic advancement along these trajectories will empower MIT to transcend its role as a “static recognition material” and evolve into an intelligent, adaptive, and systematic biomedical platform. Such evolution will accelerate the translation of MIT innovations from laboratory to clinic and industry, propelling progress in personalized medicine, point-of-care diagnostics, and synthetic biology, and yielding profound scientific and societal impact.

    Applications of molecularly imprinted solid-phase microextraction coupled with chromatography/mass spectrometry for determination of drug residues
    YAN Jingyi, HUANG Jingying, PENG Siyuan, MAN Mingsan, SUN Dani, LIU Ping, CHEN Lingxin, LI Jinhua, FAN Huaying
    2026, 44 (2):  151-168.  DOI: 10.3724/SP.J.1123.2025.06034
    Abstract ( 41 )   HTML ( 5 )   PDF (1111KB) ( 11 )  

    Drugs play an indispensable role in the fields of medicine, agriculture, and animal husbandry. However, their long-term and improper use may lead to drug residues in food, the environment and organisms, posing a potentially serious threat to human health and the ecological environment. For instance, antibiotic residues may induce bacterial resistance, pesticide residues may cause neurotoxicity, and hormone drugs may interfere with the endocrine system. Therefore, developing sensitive and accurate detection methods for drug residues has become an important prerequisite and current hot topic in drug research. Meanwhile, the complicated matrices and low contents of the residues make it necessary for the widely used chromatography/mass spectrometry (MS) determination technologies to be coupled with efficient sample pretreatment procedures. Molecularly imprinted solid-phase microextraction (MI-SPME) technology combines the rapidity, high efficiency and solvent-free characteristics of SPME, and the specific recognition and selective adsorption capabilities of molecularly imprinted polymers (MIPs), and shows significant advantages in the highly selective separation and enrichment of drug residues in complex samples. In recent years, the MI-SPME technology has become a research hotspot in the field of drug residue detection.This work systematically reviews the research progress since 2019 on the application of MI-SPME coupled with chromatography/MS in drug residue detection across food safety, environmental monitoring and biomedical fields. First, this work introduces in detail on the working principle and operation process of SPME technology. SPME achieves efficient enrichment of target analytes through the selective adsorption of the stationary phase-coated fibers, offering simplicity, speed, minimal solvent use, and compatibility with analytical instruments such as chromatography/MS.Next, the review focuses on elaborating the preparation methods and new technologies and strategies of MIPs. The traditional methods for preparing MIPs mainly include free radical polymerization, in-situ polymerization and sol-gel methods. However, traditional MIPs have defects such as template leakage risk, limited binding ability, and irregular material morphology, which restrict the application range. To this end, researchers have developed a series of novel preparation technologies and strategies, such as surface imprinting, nanoimprinting, dummy template imprinting, multi-template imprinting, multifunctional monomer imprinting and stimulus-response imprinting. These technologies and strategies have significantly enhanced the recognition and enrichment ability of MIPs for trace drug residues in complex samples by optimizing their structures and performances.To meet the requirements of different sample types and analytical instruments, MI-SPME media need to be designed into specific technical configurations through chemical or physical methods. This review summarizes six different MI-SPME device modes: MIPs-coated fiber SPME, MIPs in-tube SPME (IT-SPME), MIPs stir bar sorptive extraction (SBSE), MIPs dispersive SPME (DSPME), MIPs thin-film SPME (TFME), and MIPs in-tip SPME. Each mode offers unique advantages for the separation, enrichment and determination of drug residues in real samples. For example, the coated fiber SPME is simple to operate and suitable for direct immersion or headspace extraction of liquid samples; IT-SPME features miniaturization and automation, with excellent compatibility with chromatographic and mass spectrometric systems; DSPME achieves efficient separation and enrichment by dispersing adsorbents directly into sample solutions.Then, the applications of MI-SPME in the fields of food safety, environmental monitoring and biological medicine are summarized, highlighting typical research examples. In the field of food safety, MI-SPME can be used to detect pesticide residues, veterinary drug residues, and drugs for human use in fruits, vegetables, animal meats and dairy products. In environmental monitoring, it can be used for the detection of drug residues in aqueous environments and soil. In the field of biological medicine, it can be used for the analysis of drug residues in biological samples such as plasma, urine, and serum.Although the MI-SPME technology has shown great potential in drug residue detection, it still faces some challenges. For example, the preparation process of MIPs needs to be further optimized to improve their selectivity and stability; the development and application of new materials (such as graphene, metal-organic frameworks) for composite MIPs still need to solve problems such as high cost and complex processes; the integration of MI-SPME technology and automated equipment is also a bottleneck and important direction for future development. Looking ahead, with the advancement of green chemistry principles and point-of-care testing technologies, MI-SPME is expected to play an even greater role in drug residue detection. It will provide more efficient and precise technical support for food safety, environmental monitoring, and biomedical research.

    Research progress on the application of molecularly imprinted nanozymes in the field of biosensing
    ZHANG Xuan, LIU Shucheng, PAN Jianming
    2026, 44 (2):  169-179.  DOI: 10.3724/SP.J.1123.2025.06023
    Abstract ( 35 )   HTML ( 5 )   PDF (1427KB) ( 17 )  

    Enzymes, as biological catalysts, have garnered significant interest due to their exceptional efficiency and specificity. However, the fragility of natural enzymes under varying temperature and pH conditions significantly restricts their broader utilization. In the past few years, noteworthy advancements have been achieved in creating biomimetic enzyme systems. Scientists have effectively designed artificial enzyme-mimicking systems that exhibit outstanding performance through the integration of various components, including small molecule compounds, deoxyribonucleic acid, and nanomaterials. These systems not only exhibit remarkable catalytic efficiency but also offer considerable benefits, such as adjustable activity, simplicity in modification, and enhanced stability and reusability. Nanomachines, as a new type of enzyme analogues, specifically refer to nanomaterials with enzyme-like catalytic functions. They have played a significant role in the development of biomimetic enzyme systems. Since the first report in 2007 that iron oxide nanoparticles have peroxidase (POD) mimicking activity, hundreds of nanomaterials have been confirmed to have catalytic activities similar to those of natural enzymes such as POD and oxidase (OXD). These novel enzyme analogues not only exhibit a wide range of enzyme-like activities and structural similarity to natural enzymes, but also possess unique nanomaterial characteristics, making their catalytic activities controllable and stable. As effective substitutes for natural enzymes, nanomachines have been widely applied in fields such as biosensing, medical treatment, and environmental remediation. While every cutting-edge technology presents certain limitations, nanozymes are not an exception. They encounter notable challenges, especially concerning substrate selectivity, which is essential for effective targeted catalysis and widespread applicability. To address the aforementioned imitation, researchers have been investigating effective approaches to improve the catalytic selectivity of nanozymes. Primarily, two methods are utilized to achieve selective bioanalysis based on nanozyme catalysis: the first method involves merging nanozymes with biological recognition factors (such as natural enzymes, antibodies, DNA strands, and aptamers), while the second focuses on developing nanozymes that possess intrinsic catalytic specificity through techniques like structure-mimetic design, surface modifications, or molecular imprinting. Incorporating external biological recognition elements can undermine both the stability and cost-effectiveness of nanozymes. Additionally, the methods available for the effective conjugation of nanozymes with biological components are still in their infancy. The creation of structure-mimetic nanozymes tends to be intricate and requires meticulous regulation. In contrast, a straightforward and accessible method for generating substrate recognition sites on nanozymes is the application of molecular imprinting technology (MIT). MIT replicates interactions between enzyme substrates or antibody-antigen pairs to fabricate a cavity that is precisely shaped and sized for a particular template molecule, thus facilitating accurate molecular recognition. Due to its exceptional specificity, stability, and reproducibility, MIT is widely utilized in various fields such as biosensing, medical diagnostics, pharmaceutical assessment, sample preparation, and fluorescent detection. Moreover, the inherent advantages of molecularly imprinted polymers (MIPs), such as their economical nature, exceptional selectivity, remarkable thermochemical resilience, and the removal of the need for biologically derived techniques, have rendered molecular imprinting a feasible strategy for mimicking the roles of natural enzymes. Natural enzymes exhibit substrate specificity primarily due to the three-dimensional structure of their active sites. These active sites are meticulously shaped to ensure a perfect match with the spatial configuration of the intended substrate. Following this concept, molecular imprinting nanoenzymes cleverly integrate molecular imprinting techniques with the properties of nanoenzymes, allowing biomimetic catalysts to retain catalytic selectivity while also demonstrating remarkable substrate specificity. This paper first summarizes the fundamental characteristics of nanozymes, then elaborates on the conventional preparation processes for molecularly imprinted nanozymes, and thoroughly explores the impact of molecular imprinting on the catalytic performance of nanozymes. Through an analysis of typical cases, the latest research advancements in molecularly imprinted nanozymes biosensing field are introduced. Finally, this paper discusses the challenges encountered and future development directions in this area, aiming to provide theoretical references and practical guidance for the application of molecular imprinting and nanozymes in biosensing.

    Application of molecularly imprinted polymers-based sensors for determination of acute coronary syndrome biomarkers
    ZHANG Yufan, XIA Jingwen, ZHU Jiayuan, ZENG Maosheng, BAI Jingyi, XU Qin, GAO Hang
    2026, 44 (2):  180-190.  DOI: 10.3724/SP.J.1123.2025.08003
    Abstract ( 118 )   HTML ( 4 )   PDF (1097KB) ( 20 )  

    Cardiovascular diseases (CVDs) are among the leading cause of global morbidity and mortality. Due to their high prevalence and often asymptomatic progression, there is a pressing need for diagnostic tools that enable the early, accurate, and accessible detection of them. Acute coronary syndrome (ACS), as a common and severe CVDs with high morbidity and mortality rates, has attracted considerable scientific interest. Various methods have been developed to detect ACS rapidly and accurately. Traditional diagnostic methods relying on antibody-based assays are effective. However, they face significant limitations, including high production costs, poor stability under varying environmental conditions, batch-to-batch variability, and cross-reactivity leading to false positives. These challenges have motivated the search for robust, cost-effective alternatives capable of detecting biomarkers with high sensitivity and specificity. Molecularly imprinted polymers (MIPs) have emerged as a promising alternative solution, offering antibody-like molecular recognition capabilities, superior stability, lower production costs, and resistance to harsh environmental conditions. This review systematically examines the latest advancements in MIP-based sensors for ACS biomarker detection in the last fifteen years, including imprinting strategies for key ACS biomarkers, sensor development and integration, and current challenges along with future perspectives. The first section focuses on the molecular imprinting techniques for essential ACS biomarkers, such as cardiac troponin (cTnI/cTnT), myoglobin (Myo), and creatine kinase (CK). It compares whole-protein imprinting with epitope imprinting, highlighting the advantages of the latter in reducing template costs and enhancing binding specificity. Epitope imprinting using short peptide sequences has demonstrated femtomolar detection limits while overcoming challenges associated with large protein templates, such as structural denaturation and difficult template removal. The review also explores innovative approaches like dummy template imprinting, where structurally similar but cheaper molecules are used to create MIPs for high-cost biomarkers, achieving comparable specificity and sensitivity. The second section discusses the integration of MIPs with advanced biosensing platforms. Electrochemical sensors, using MIP-modified electrodes, have achieved remarkable sensitivity and rapid response times, making them suitable for point-of-care testing (POCT). Optical sensors, particularly those based on surface-enhanced Raman spectroscopy and surface plasmon resonance, enable label-free, real-time detection with ultra-low detection limits. The review also addresses the integration of MIPs with microfluidic technology, where miniaturized devices facilitate automated, high-throughput biomarker analysis. Examples include paper-based microfluidic sensors that combine capillary action with MIP-SERs tags for multiplexed detection, achieving low detection limits without complex instrumentation. Despite these advancements, the review identifies key challenges hindering widespread clinical adoption of the MIP’s based ACS sensor. Although the sensitivity and specificity of MIPs are impressive, they still lag behind those of monoclonal antibodies in some applications, particularly for low-abundance biomarkers. Reproducibility issues arise from variations in polymerization conditions and template removal efficiency. Commercialization barriers include the lack of standardized production protocols and regulatory frameworks for MIP-based diagnostics. The review proposes several strategic directions to address these limitations. Computational modeling and machine learning could optimize monomer selection and polymerization conditions to enhance MIP’s performance. The development of hybrid systems combining MIPs with nanomaterials may further improve sensitivity and signal transduction. Multidisciplinary collaborations among chemists, engineers, and clinicians will be essential to translate laboratory innovations into commercially viable diagnostic tools. Additionally, the integration of MIPs with artificial intelligence machine learning algorithms could support the development of personalized diagnosis and treatment strategies. These future perspectives are likely to have a significant impact on the early diagnosis and treatment of cardiovascular diseases. In conclusion, MIP-based sensors represent a promising direction in ACS diagnostics, offering a unique combination of affordability, stability, and precision. By addressing current technical and translational challenges, MIP technology has the potential to revolutionize early disease detection, particularly in resource-limited areas. This review not only summarizes a decade of research progress but also provides a plan for future developments that could make personalized, decentralized cardiovascular diagnostics a widespread reality.

    Articles
    Preparation of superhydrophilic imprinted resin-graphene aerogel composite and its precise recognition of tumor biomarker in urine
    WANG Mingwei, TIAN Tao, BAI Ligai, HAN Dandan, YAN Hongyuan
    2026, 44 (2):  191-200.  DOI: 10.3724/SP.J.1123.2025.05021
    Abstract ( 62 )   HTML ( 5 )   PDF (1606KB) ( 26 )  

    In recent years, molecularly imprinted polymers have shown considerable promise in analytical detection and early diagnosis of diseases due to their high selectivity and specificity. Nevertheless, the practical implementation of these methods is still restricted by several intrinsic limitations associated with traditional synthesis approaches, including a strong reliance on organic solvents, poor recognition efficiency in aqueous media, and low adsorption capacity. To overcome these challenges, this study presents an innovative strategy that integrates superhydrophilic resin with graphene aerogel (GA), resulting in successful fabrication of a superhydrophilic molecularly imprinted resin-GA composite (HMIR-GA) via surface in situ polymerization in water. The resulting HMIR-GA exhibited a significantly enhanced adsorption capacity and improved recognition performance in aqueous environments towards tumor biomarker. Characterization of the HMIR-GA was performed using Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), nitrogen adsorption-desorption analysis, and contact angle measurements. FT-IR spectra revealed that the broad peak at 3 400 cm-1 can be ascribed to the formation of –OH associations. The absorption peak at 1 724 cm-1 corresponds to the stretching vibration peak of C=O on the surface of graphene oxide (GO). The absorption peaks at 1 602 cm-1 and 1 462 cm-1 are assigned to the C=C stretching vibration peaks of resorcinol. During the reaction process, due to the reduction effect of ammonia water, the C=O on graphene oxide is reduced. The characteristic peak at 1 069 cm-1 is induced by the stretching vibration of C-O-C, representing the formation by the reaction between resorcinol and hexamethylenetetramine. These characteristic peaks clearly demonstrate that the HMIR have been successfully incorporated into the graphene aerogel. The FT-IR results confirm the successful synthesis of HMIR-GA. SEM reveals that the surface of graphene oxide exhibits a wrinkled lamellar structure. In contrast, the fabricated HMIR-GA and superhydrophilic molecularly non-imprinted resin-GA composite (HNIR-GA) display a loose and porous architecture, indicating that the synthesized HMIR has been successfully grown onto the graphene aerogel. The porous structure is conducive to the rapid adsorption of 5-hydroxyindoleacetic acid (5-HIAA), which is beneficial for enhancing the performance of relevant applications. The Brunauer-Emmett-Teller (BET) specific surface areas of HMIR-GA and HNIR-GA are 95.1 m²/g and 44.5 m²/g, respectively. The pore volumes are 0.31 cm³/g and 0.20 cm³/g, respectively. In comparison with HNIR-GA, HMIR-GA possesses a larger specific surface area and pore volume, which is conducive to enhancing its adsorption capacity for 5-HIAA. To evaluate the hydrophilicity of HMIR-GA and HNIR-GA, contact angle measurements were performed. The results showed that when water droplets were placed on the surfaces of these two materials, they rapidly spread and fully wetted the surfaces within 0.07 s, indicating that HMIR-GA and HNIR-GA exhibited superior hydrophilic properties. This enhanced hydrophilicity facilitates the effective adsorption and extraction of the tumor biomarker 5-HIAA from urine samples. Static and competitive adsorption experiments revealed that HMIR-GA has a strong affinity for 5-HIAA. The evaluation of adsorption kinetics was carried out by employing both the pseudo-first-order and pseudo-second-order models, indicating a better fit with the pseudo-second-order model (R²=0.999 3), suggesting that chemisorption is the dominant mechanism. Furthermore, equilibrium adsorption data were analyzed using the following models—Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich (D-R). The best fit was achieved with the Freundlich isotherm model (R²≥0.985 2), indicating multilayer adsorption on heterogeneous surfaces. A highly sensitive method for precise determination of 5-HIAA was established by employing HMIR-GA as a pipette tip solid-phase extraction adsorbent coupled with high performance liquid chromatography. The calibration curve exhibited excellent linearity across the mass concentration range of 0.02–40.0 μg/mL (r=0.999 8). The limits of detection (LOD) and quantification (LOQ) were 3.7 ng/mL and 12.3 ng/mL, respectively, based on signal-to-noise ratios of 3 and 10. Method accuracy was verified through recovery tests at spiked mass concentrations of 0.1, 1.0, and 10.0 μg/mL, yielding recoveries between 75.7% and 92.5% with relative standard deviations (RSDs) below 3.4%. Precision assessments via intra-day and inter-day tests yielded RSDs of 2.9% and 4.1%, respectively (n=6). Finally, the developed method was applied for the determination of 5-HIAA levels in real urine samples. This work not only provides a robust and environmentally friendly strategy for the fabrication of functionalized molecularly imprinted polymers but also shows great promise for clinical applications, offering crucial technical support for early diagnosis of gastroenteropancreatic neuroendocrine tumors.

    Tripeptide polymer-based cell-imprinted hydrogels for high-efficiency circulating tumor cell capture
    SUN Wenjing, ZHANG Zhiyuan, ZHAO Xinmiao, CHEN Jinghua, QING Guangyan
    2026, 44 (2):  201-213.  DOI: 10.3724/SP.J.1123.2025.05002
    Abstract ( 43 )   HTML ( 5 )   PDF (2030KB) ( 15 )  

    Circulating tumor cells (CTC) have emerged as crucial mediators in the metastatic cascade, offering invaluable insights as real-time liquid biomarkers for cancer progression, prognosis, and treatment response. Their exceptionally low concentration in peripheral blood, which typically ranges from a handful to a few dozen cells per milliliter amidst billions of background blood cells, poses formidable challenges for isolation and molecular characterization. Despite this, the efficient and specific capture of CTC holds tremendous potential for revolutionizing early cancer detection, dynamic monitoring of therapeutic efficacy, and guiding personalized treatment strategies. Currently, the primary technologies for CTC enrichment fall into two categories: immunoaffinity-based methods that employ antibodies targeting epithelial surface markers such as epithelial cell adhesion molecule (EpCAM), and label-free approaches that leverage physical properties including cell size, deformability, and density, exemplified by membrane filtration and centrifugal techniques. However, these conventional methods are hampered by several inherent limitations, including high operational costs, dependence on highly variable surface antigen expression, insufficient capture specificity leading to low purity, and significant interference from heterogeneous blood components such as leukocytes and platelets. Consequently, there is an urgent and growing need to develop novel functional materials and platforms that offer enhanced selectivity, robust stability in physiological conditions, excellent biocompatibility, and improved clinical applicability for the effective isolation and analysis of CTC. In this study, we innovatively integrate cell imprinting technology with a rational amino acid-based affinity strategy to develop a tryptophan-histidine-arginine (WHR) tripeptide-functionalized cell-imprinted hydrogel for highly efficient and selective capture of CTC. The design leverages the unique properties of mesoporous silica nanoparticles (MSN) as carriers, which are first synthesized and then surface-modified with epoxy groups via silane coupling agents. The WHR tripeptide is subsequently grafted onto the MSN surface through a ring-opening reaction, yielding the WHR@SiO₂ composite material. This material demonstrates strong and specific binding affinity toward sialic acid (Neu5Ac) and sialylated glycopeptides (SGP), which are overexpressed on the surface of many cancer cells. Building on this molecular recognition capability, a three-dimensional cell-imprinted hydrogel is fabricated using poly(ethylene glycol) dimethacrylate (PEGDMA) as the cross-linking backbone via free radical polymerization. The hydrogel is molded against SMMC-7721 template cells to create cavities that complement the target cells in size, shape, and surface topology, thereby enhancing capture efficiency through both physical and biochemical matching. Experimental results demonstrate that the WHR-modified hydrogel achieves a remarkable capture efficiency of up to 94% for SMMC-7721 cells, significantly outperforming hydrogels modified with individual amino acids such as tryptophan, histidine, or arginine alone. The system also exhibits excellent hemocompatibility, with minimal adsorption of human serum albumin (HSA), below 5%, indicating superior anti-fouling properties in biological environments. In vitro cytotoxicity assessments confirm high biocompatibility, with cell viability exceeding 90% after 48 h of co-culture. Further characterization through scanning electron microscopy (SEM) and atomic force microscopy (AFM) reveals well-defined surface imprints that mirror the morphology of template cells, confirming the successful integration of topographical cues. The synergy between the physical structure of the imprinted cavities and the biochemical affinity of the WHR tripeptide is identified as the key factor contributing to the high capture performance, even at low cell concentrations (as few as 100 cells/mL). In conclusion, this work presents a robust and efficient platform for CTC capture that combines cell imprinting for morphological recognition with WHR-mediated affinity for sialylated glycoproteins. The hydrogel demonstrates high selectivity, stability, and biocompatibility, offering a promising tool for clinical applications in liquid biopsy and early cancer detection. The modular design of the system also allows for adaptation to other cancer types by altering the peptide sequence or template cells, highlighting its broad potential in cancer research and diagnostics.

    Design of ZIF-L-based boronate affinity molecularly imprinted material and its application in the detection of ribavirin in environmental water
    QI Wanting, TONG Yukui
    2026, 44 (2):  214-222.  DOI: 10.3724/SP.J.1123.2025.04033
    Abstract ( 8 )   HTML ( 4 )   PDF (1488KB) ( 3 )  

    Ribavirin (RBV) is a broad-spectrum antiviral drug. It is widely used to treat various viral infections. However, its entry into water bodies can cause serious harm to both the ecological environment and human health. Thus, there is an urgent need for a simple and efficient method to detect RBV for detection purposes. In this study, a two-dimensional ZIF material (ZIF-L) served as the matrix, RBV as the template molecule, and 3-aminophenylboronic acid (APBA) as the functional monomer, using its self-polymerization ability to form a molecularly imprinted layer on the surface of ZIF-L. Imprinted cavities were created using a MeOH-HAc (1∶1, volume ratio) eluent to disrupt the interaction between RBV and APBA, yielding ZIF-L-based boronate affinity molecularly imprinted polymers (ZIF@B-MIPs). Non-imprinted materials (ZIF@B-NIPs) were prepared identically without RBV. ZIF@B-MIPs features dynamic recognition sites formed through pH-responsive boronate ester bonds. This enabled synergistic recognition based on the template molecule’s “shape memory” and “chemical bonding”. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FT-IR) were employed to characterize the morphology and functional groups of the material. Notably, new FT-IR peaks emerged for ZIF@B-MIPs at 1 381 cm-1 (B-O vibration) versus ZIF-L, confirming APBA polymerization. This indicates that the polymerization of APBA onto the surface of ZIF-L was successful. The synthesis and adsorption conditions were optimized. The results showed that, with a ZIF-L dosage of 100 mg, the optimal amount of the self-polymerizing reagent APBA was 100 mg. A self-polymerization time of 5 h was sufficient to form an appropriately thick imprinted layer. At pH 8.5, the stability of the polymer network was maintained while the imprinting effect and mass transfer efficiency were maximized. The post-elution re-adsorption capacity retention rate reached 96.8%, balancing elution efficiency with structural integrity. A RBV mass concentration of 60 mg/L was selected for the experimental requirements. After optimization, the saturation adsorption capacity of ZIF@B-MIPs for RBV reached 21.43 mg/g. The imprinting factor (IF) was 5.32. The material’s performance was assessed through adsorption and reusability experiments. The results indicated that the material possesses good specificity and selective recognition ability. It also exhibits a rapid adsorption rate and good reusability. The adsorption experiment results showed that the adsorption kinetics followed the pseudo-second-order model (R2=0.995 3). Adsorption equilibrium was achieved within 15 min. The adsorption process of RBV by the adsorbent involves chemisorption. The Langmuir isotherm adsorption model (R2=0.982 5) fitted the experimental data better. This indicates that the adsorption of RBV by ZIF@B-MIPs likely involves monolayer adsorption. In mixed solutions of RBV and three interfering substances (lamivudine,uridine,inosine) with mass concentration ratios of 1∶1 and 1∶10, the adsorption capacity of RBV by ZIF@B-MIPs remained high. The interfering substances had minimal impact on the adsorption performance. The reusability experiment results showed that the material retained 93.6% of its initial adsorption capacity after six adsorption-desorption cycles. The reproducibility of ZIF@B-MIPs was investigated using six batches of adsorbents. The adsorption capacity for RBV ranged from 19.41 to 20.73 mg/g. This indicates that the material also possesses good reproducibility. In the detection of actual environmental water samples, the method exhibited excellent applicability. The recoveries of RBV in environmental water samples at three spiked levels (30, 50, 60 mg/L) were 83.8%-94.5% (RSD<2.1%). The detection system constructed in conjunction with high performance liquid chromatography (HPLC) demonstrated a good linear relationship in the range of 0.05 to 100 mg/L (R2=0.991 6). The limit of detection was 0.038 mg/L (S/N=3), and limit of quantification was 0.081 mg/L (S/N=10). The ZIF@B-MIPs-HPLC technology was successfully applied to the efficient adsorption, enrichment, and detection of RBV in drinking water sources. It holds potential for applications in the fields of human health and environmental protection. This technology offers a new strategy for the rapid detection of trace antiviral drugs in environmental samples.