Yongqin Lv

Vimentin is a cytoskeletal protein upregulated during epithelial‐mesenchymal transition that can also be aberrantly displayed on the surface of multiple tumor cell types, making it a promising target for tumor imaging. Here, we develop epitope‐imprinted polymer nanoparticles (nanoMIPs) for vimentin recognition through a two‐step strategy comprising screening a library of non‐imprinted nanoparticles to identify a lead formulation, followed by peptide‐directed molecular imprinting. The resulting nanoMIPs exhibited enhanced apparent affinity for vimentin, with picomolar‐range K _D values, although these values represent model‐dependent ensemble apparent affinities that may include contributions from multiple nanoparticle‐ligand contacts and local rebinding rather than intrinsic monovalent affinities. The nanoMIPs preferentially bound cancer cells presenting cell‐surface vimentin in vitro. The enhanced target binding and reduced off‐target binding were consistent with an imprinting‐associated improvement in molecular discrimination, although nonspecific physicochemical interactions were not completely eliminated. These findings extend epitope‐guided nanoMIP design to structurally dynamic, cell surface‐associated cytoskeletal targets, and support the development of synthetic receptors for tumor imaging. In vivo, the optimized nanoMIPs produced a tumor‐associated fluorescence signal approximately 1.44 times that of the matched non‐imprinted nanoparticles.

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 （K_D） 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.

Molecularly imprinted membranes (MIMs) epitomize the convergence of membrane science with molecular imprinted technology. Endowed with intrinsic molecular recognition and memory functionalities, MIMs have the potential to evolve into pivotal tools for the selective separation, identification, and purification of biomolecules. This review summarizes the forefront advancements in the selective recognition and separation of macromolecular biomarkers through MIMs, such as proteins, peptides, and nucleotides. A comprehensive overview of diverse imprinting polymerization methodologies employed in crafting MIMs tailored for specific biomacromolecule targets is presented. Additionally, the evolving research landscape concerning MIMs as a potent platform for the targeted capture of biomacromolecule-associated biomarkers is critically appraised and is discussed.

The upcycling of carbon dioxide (CO ₂ ) into value‐added chemicals offers a compelling strategy for sustainable carbon utilization. However, the efficient synthesis of energy‐dense, long‐chain molecules remains a significant challenge. Here, a spatially decoupled electro‐biosystem integrating CO ₂ electrolysis with microbial fermentation is presented to produce high‐value chemicals. A catalytic platform using tannic acid‐Cu ²⁺ metal‐phenolic networks is developed to spatially confine the synthesis of Ag and Cu ₂ O nanoparticles within a covalent‐organic polymer, creating tandem catalytic sites. This design significantly enhances CO ₂ ‐to‐ethanol selectivity (Faradaic efficiency: 44.5%) and boosts current density to 400 mA cm ⁻² . A compact membrane electrode assembly reactor (5×5 cm ² ) enables ethanol production in pure water, which is further converted by engineered Escherichia coli into itaconic acid, isopropanol, and polyhydroxybutyrate. The modular design optimizes electrochemical reduction and microbial bioconversion, reducing metabolic burdens and improving efficiency, offering a scalable, adaptable biohybrid platform for CO ₂ valorization.

Prostate‐specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and tumor vasculature, making it an important biomarker. However, conventional PSMA‐targeting agents like antibodies and small molecules have limitations. Antibodies exhibit instability and complex production, while small molecules show lower specificity and higher toxicity. Herein, this work develops a novel PSMA‐targeting synthetic antibody to address prior limitations. This work synthesizes fluorescently labelled, N‐isopropylacrylamide‐based epitope imprinted nanogels (MIP‐M) using a dispersion of magnetic nanoparticles as template carriers with a linear epitope from PSMA's extracellular apical domain as the template. MIP‐M demonstrates high binding affinities for both the epitope template (apparent K_D = 6 × 10⁻¹⁰ м) and PSMA (apparent K_D = 2.5 × 10⁻⁹ м). Compared to reference peptides and human serum albumin, MIP‐M indicates high specificity. Flow cytometry and confocal laser scanning microscopy comparing cell lines displaying normal (PC3) and enhanced (LNCaP) PSMA expression levels, revealed that MIP‐M and a PSMA antibody exhibits comparable binding preferences for the latter cell line. Moreover, MIP‐M demonstrates selectivity on par with the PSMA antibody for targeting PSMA‐positive prostate tumor over normal tissue, enabling discrimination. This MIP‐M addresses stability, production, specificity and toxicity limitations of prior targeting agents and offer a promising alternative for PSMA‐directed cancer diagnosis and treatment.

Molecularly imprinted polymers (MIPs) show significant promise as effective alternatives to antibodies in disease diagnosis and therapy. However, the challenging process of screening extensive libraries of monomer combinations and synthesis conditions to identify formulations with enhanced selectivity and affinity presents a notable time constraint. The need for expedient methods becomes clear in accelerating the strategic development of MIPs tailored for precise molecular recognition purposes. In this study, an innovative high‐throughput screening methodology designed to identify the optimal MIP formulation for targeting tumors is presented. Employing a microtiter plate format, over 100 polymer syntheses are conducted, incorporating diverse combinations of functional monomers. Evaluation of binding performance utilizes fluorescence‐based assays, focusing on an epitope of the epidermal growth factor receptor (EGFR). Through this meticulously structured screening process, synthesis conditions that produced MIP nanoparticles exhibiting substantial specificity for EGFR targeting ( K _D = 10 ⁻¹² m ) are identified. These “bionic antibodies” demonstrate selective recognition of cancer cells in whole blood samples, even at concentrations as low as 5 cells mL ⁻¹ . Further validation through fluorescent imaging confirms the tumor‐specific localization of the MIPs in vivo. This highly efficient screening approach facilitates the strategic synthesis of imprinted polymers functioning as precision bioprobes.