Exploiting the bioengineering versatility of lactobionic acid in targeted nanosystems and biomaterials

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Lactobionic acid (LBA) has rapidly emerged as a strategic functionalization molecule in the development of nanoparticle-based platforms and biomaterials with promising therapeutic applications. Exploiting the multi-functionality of LBA has enabled to expand the drug loading, release and selective cellular uptake capacity of hepatoma-targeting chemotherapy and nanoparticle-based theranostic systems. The high liver-specificity displayed by LBA-conjugated dendrimers, micelles and nanoparticles has indeed reinforced the great potential of LBA in fine-tuning the surface engineering of promising drug carriers to combat hepatocellular carcinoma. Additionally, its cytocompatibility, selectivity and functionality confer unique properties to design synthetically engineered matrices with enhanced liver-specificity for liver tissue engineering applications. Notably, the biospecific identification and biochemical cross-linking specificity found with the asialoglycoprotein receptor (ASGPR) have converted LBA into the perfect cell-targeting ligand for strengthening the recognition between novel designed nanocarriers and hepatocytes at cellular level. The present review overviews the latest advances in the galactosylation of target-specific nanocarriers and polymers via LBA functionalization with an emphasis on the great bioengineering versatility offered by this polyhydroxy bionic acid in the preparation of next-generation tools ranging from contrast imaging agents to galactosylated scaffolds for the diagnosis and treatment of hepatic diseases. Perspectives on the bioengineering approaches that can foster the design of multi-functional LBA-conjugated therapeutic nanoplatforms are also discussed.Graphical abstractHighlightsLactobionic acid offers unique specificity in targeted liver cancer chemotherapy.Cell internalization is unlocked via lactobionic acid functionalization.Lactobionic acid grafting enables specific targeting of hepatocarcinoma cells.Lactobionic acid modulates hepatocyte adhesion in liver tissue engineering approaches.Lactobionic acid supports spheroid formation with enhanced liver-specific functions.

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