:
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 the 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 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 progresses about HA-based multidrug nano-carriers for combination cancer therapy are summarized and its potential challenges for translational applications have been discussed.
