Recent advances in hyaluronic acid-based nanomedicines: Preparation and application in cancer therapy

Rapid development of stimuli-responsive drug delivery systems (DDSs) for tumor therapy has raised increasing interest in recent decades, and many nanomedicines are prepared to achieve accurate or sustained drug release. However, the fabrication process for these nanomedicines has been far too intricate and their potential biosafety has not been fully understood, which has hampered their clinical translation. Challenges for developing DDSs remain on balancing the complexity of the fabrication process with their translational feasibility. Owing to water-solubility, biocompatibility, biodegradability and CD44-targetability, hyaluronic acid (HA) as a versatile building block has gained great popularity due to a simplified fabrication process and unique characteristics of HA for DDSs. In this review, we overviewed the biological function and multiple chemical modifications of HA, and discussed the fabrication of HA-based drug delivery systems (HA-DDSs) with specific tumor microenvironmental stimuli-responsive linkers. We systemically surveyed the applications of HA-DDSs for chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, gene delivery and combination therapy.