Advances and clinical perspectives of boronate affinity-driven glycoproteomics: A review

Glycoproteomics has emerged as a powerful tool for decoding cellular communication and disease mechanisms. However, the structural complexity and low abundance of glycoproteins demand high-efficiency enrichment materials. Conventional methods such as lectin affinity, hydrazide chemistry, metal ion affinity, and hydrophilic interaction chromatography have been widely used, but they suffer from drawbacks including limited specificity, harsh chemical conditions, or nonspecific adsorption. These constraints restrict their utility for complex biological specimens and impede clinical translation. Boronate affinity materials, which enable reversible and selective binding to cis-diol moieties, present a promising alternative for glycoprotein isolation.

Recent advances in boronate-affinity materials have led to notable improvements in specificity, stability, and biocompatibility, substantially broadening their applicability in glycoproteomics. Mesoporous frameworks provide high surface areas and tunable pores that enhance adsorption capacity and facilitate efficient capture of glycoproteins. Boronate-functionalized nanocomposites exhibit superior responsiveness to physiological pH and temperature, ensuring stable performance in complex biological environments. Molecularly imprinted polymers, with their tailor-made recognition sites, achieve exceptional selectivity toward glycoprotein motifs. Together, these innovations enable high-throughput, sensitive, and reproducible enrichment of glycoproteins, even from challenging samples such as plasma, cerebrospinal fluid, and exosomes. Importantly, enrichment via these strategies has facilitated the identification of clinically relevant glycoprotein biomarkers associated with cancer, neurodegenerative disorders, and metabolic diseases. Moreover, the integration of boronate affinity enrichment with advanced analytical techniques, such as mass spectrometry and microfluidics, further underscores its potential to improve diagnostic accuracy and accelerate clinical translation in precision medicine.

This review highlights the unique advantages of boronate affinity materials in addressing the limitations of conventional glycoprotein enrichment. Their efficiency, specificity, and clinical adaptability not only facilitate biomarker discovery but also promote the integration of glycoproteomics into next-generation precision diagnostics. In addition, by summarizing the design principles, functional mechanisms, and biomedical applications of these materials, this review provides a framework to support their further development and clinical translation.