[Molecular imprinting strategies and advances targeting biomembranes]

Biomembranes are selective barriers and communication interfaces between intracellular and extracellular environments. They are crucial for signal transduction， energy transfer， and material exchange. Composed of lipids， proteins， glycans， and other components， biomembranes are central platforms for cell recognition and communication. Their specific recognition and binding abilities show great potential in early disease diagnosis， targeted drug delivery， environmental monitoring， and more. Molecularly imprinted polymer （MIP） has emerged as a robust tool for recognizing and binding biomolecules on biomembranes. This article summarizes recent technological advancements in MIP for biomembrane-associated lipids， proteins， and glycans. Lipids are a key part of biomembranes， crucial for maintaining membrane fluidity and stability. In lipid imprinting， lipid bilayers serve as templates. Functional monomers interact with lipid molecules and， upon polymerization， form a polymeric shell on the bilayer. Template removal leaves behind complementary binding sites. This strategy has been exploited to fabricate lipid-imprinted nanoparticles for drug delivery. These nanoparticles selectively recognize lipid components on cell membranes， thereby enabling targeted drug delivery. Proteins constitute another critical class of biomembrane components and execute diverse functions. Protein-imprinted MIPs selectively recognize membrane proteins such as cell-surface receptors， bacterial outer-membrane proteins， and viral capsid proteins. This enables precise identification and binding of specific proteins， which is useful in disease diagnosis and drug development. MIP can detect specific membrane protein biomarkers on cancer cells， allowing for early cancer detection and monitoring. Glycans also play a key role in biomembranes， particularly in cell recognition and immune responses. Carbohydrate-imprinted MIPs recognize specific glycan structures for use in disease diagnosis and therapy. Cancer cells have different glycan structures on their membranes compared to normal cells. These abnormal glycans serve as biomarkers for early cancer detection and monitoring. The article also emphasizes the potential of MIP in various applications. In disease diagnosis， MIP can develop biosensors for fast and accurate detection of disease biomarkers， enabling early treatment. In drug delivery， MIP can create targeted systems that deliver drugs directly to diseased cells， minimizing off-target effects and enhancing therapeutic efficacy. In cell imaging， MIP can specifically label cells or biomolecules， providing detailed images of cellular processes and aiding in understanding disease mechanisms. In biosensing， MIP can serve as efficient recognition elements to construct biosensors for detecting specific biomarkers in biological samples. The specific binding sites formed by molecular imprinting technology enable MIP-based biosensors to detect target molecules with high sensitivity and selectivity， providing a powerful tool for early disease diagnosis and real-time monitoring. However， the development of MIP still faces challenges， including complex synthetic procedures， incomplete template removal， limited scalability， and the need for performance optimization. The synthesis process is complex， requiring precise control of parameters like functional monomers， cross-linkers， and initiators. Incomplete template removal compromises binding affinity and selectivity. Scaling-up while maintaining batch-to-batch reproducibility is challenging， and the binding capacity， selectivity， and stability of MIPs must be optimized for each application. For glycan imprinting， monosaccharide templates have low specificity， glycan chain templates are difficult to synthesize and purify， and there is a lack of efficient O-glycan cleavage tools. To break through the bottleneck， the study improves template removal efficiency， synthetic optimization and structural controllability through controllable free radical/photo-initiated polymerization， magnetic material integration， microfluidics， artificial intelligence， machine learning and 3D printing； meanwhile， virtual templates， glycopeptide substitution templates， and solid-phase imprinting strategies are used to solve the scarcity of glycan templates. In addition， optimization of biocompatible materials， surface modification to reduce toxicity， and combination with computer simulation and automated preparation can accelerate clinical translation. In conclusion， MIP technology is highly promising for biomembrane research with broad applications in disease diagnosis， drug delivery， cell imaging， and extracellular vesicle enrichment. With continued development and optimization， MIP are expected to play an increasingly important role in biomedical and life sciences， offering more powerful tools and solutions for disease diagnosis， treatment， and monitoring.