Hyaluronic acid hybrid nanostructures for cancer therapy

The development of targeted and stimuli-responsive nanoplatforms remains a major challenge in cancer nanomedicine. Hyaluronic acid (HA), a naturally occurring glycosaminoglycan, is widely used for tumor-targeted drug delivery because it binds CD44, a receptor overexpressed in many cancers. This review aims to examine how the design of HA-based hybrid nanostructures influences drug delivery and therapeutic performance. It discusses the integration of HA with organic and inorganic components through coordination interactions, covalent conjugation and interfacial assembly. These systems synergistically combine HA's intrinsic biocompatibility and biodegradability with the functional properties of metals, polymers, lipids, peptides and carbon nanomaterials. Particular emphasis is placed on relationships among assembly strategy, colloidal stability, drug loading and release, CD44-mediated uptake and biological outcomes. Applications in chemotherapy, phototherapy, sonodynamic therapy, gene therapy, immunotherapy, and theranostics are also summarized. Finally, receptor heterogeneity and biological barriers are considered as challenges for clinical translation.