Carbohydrate-Functionalized Liposomal Nanocarriers: Design Strategies for Receptor-Mediated Organ Targeting and Advanced Theranostic Applications

Liposomes are among the most advanced drug-delivery technologies in modern nanomedicine, with high biocompatibility, structural diversity, and surface activity. They can carry both hydrophilic and lipophilic drugs. While they have been successfully applied in drug therapy to enhance pharmacokinetics and minimize systemic side effects, traditional liposomes rely on passive targeting mechanisms, including the EPR effect, to deliver drugs to targeted sites, with a high risk of non-specific distribution in the body. In contrast, carbohydrate-functionalized liposomes represent a biologically inspired drug delivery approach that utilizes the natural specificity of carbohydrate-receptor interactions to enable organ- or cell-specific drug delivery. In this review, we provide a comprehensive review of ligand selection, surface modification, conjugation chemistry, and critical quality attributes that define biological performance and robustness in drug delivery systems. Organ-specific drug delivery systems are presented, including glucose, mannose, or chitosan-functionalized liposomes for targeting the brain, galactose or N-acetylgalactosamine-based systems for targeting hepatocytes, or hyaluronic acid, fucose, or sialic acid-functionalized liposomes for targeting tumours or immune systems, respectively. Recent advancements in multi-ligand systems, stimulus-responsive systems, or biodegradable glycan surfaces have demonstrated their potential to control glycan presentation, thus controlling drug activity in drug delivery systems. In addition, challenges in glycan-based drug delivery systems, including their synthesis, stability, or safety, have been addressed, with future research directions focusing on glycomics, receptor research, or microfluidic engineering in the development of novel biomimetic drug delivery systems with disease-responsive, organ-specific, or targeted drug delivery capabilities.