Glycodendrimers: endlessly evolving architecture design, synthetic strategies, and biological applications

The synthesis of dendritic architectures has steadily advanced to overcome challenges associated with biological applications. Key issues—including reduced toxicity, enhanced target specificity, improved stability, and efficient delivery of drugs, vaccines, and genes—have posed significant hurdles, particularly when scalability for therapeutic translation is required. Among these, optimizing dendrimer systems to engage in carbohydrate-related biological functions has remained a central focus since the introduction of glycodendrimers. The emergence of glycodendrimers has proven especially effective in contexts demanding multivalent binding interactions. This review highlights advancements in the design of multivalent carbohydrate-based nanomaterials, tracing their evolution from the early development of glycopolymers to the emergence of glycodendrimers. It presents key developments in the use of scaffolds featuring an expanded array of surface functional groups alongside variations in the chemical building blocks traditionally employed in classical dendrimer synthesis—culminating in the so-called “onion-peel strategy”. These innovations are further complemented by the integration of orthogonal ligation techniques. Additionally, efforts to streamline the synthesis of multivalent glycoarchitectures have led to the emergence of simplified methodologies, including transition-metal-templated assembly and the self-organization of glycodendrimersomes.