Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.
With the success of several clinical trials of products based on human serum albumin (HSA) and the rapid development of nanotechnology, HSA-based nanodrug delivery systems (HBNDSs) have received extensive attention in the field of nanomedicine. However, there is still a lack of comprehensive reviews exploring the broader scope of HBNDSs in biomedical applications beyond cancer therapy. To address this gap, this review takes a systematic approach. Firstly, it focuses on the crystal structure and the potential binding sites of HSA. Additionally, it provides a comprehensive summary of recent progresses in the field of HBNDSs for various biomedical applications over the past five years, categorized according to the type of therapeutic drugs loaded onto HSA. These categories include small-molecule drugs, inorganic materials and bioactive ingredients. Finally, the review summarizes the characteristics and current application status of HBNDSs in drug delivery, and also discusses the challenges that need to be addressed for the clinical transformation of HSA formulations and offers future perspectives in this field.