Hyaluronan (HA) is a natural linear polysaccharide that has excellent hydrophilicity, biocompatibility,
biodegradability, and low immunogenicity, making it one of the most attractive biopolymers
used for biomedical researches and applications. Due to the multiple functional sites on HA and its intrinsic
affinity for CD44, a receptor highly expressed on various cancer cells, HA has been widely engineered
to construct different drug-loading nanoparticles (NPs) for CD44-targeted anti-tumor therapy.
When a cocktail of drugs is co-loaded in HA NP, a multifunctional nano-carriers could be obtained,
which features as a highly effective and self-targeting strategy to combat cancers with CD44 overexpression.
The HA-based multidrug nano-carriers can be a combination of different drugs, various therapeutic
modalities, or the integration of therapy and diagnostics (theranostics). Up to now, there are many
types of HA-based multidrug nano-carriers constructed by different formulation strategies, including
drug co-conjugates, micelles, nano-gels and hybrid NP of HA and so on. This multidrug nano-carrier
takes the full advantages of HA as an NP matrix, drug carriers and targeting ligand, representing a simplified
and biocompatible platform to realize the targeted and synergistic combination therapy against
the cancers. In this review, recent progress of HA-based multidrug nano-carriers for combination cancer
therapy is summarized and the potential challenges for translational applications have been discussed.