Preparation and anti-tumor application of hyaluronic acid-based material for disulfide and copper ions co-delivery

Disulfide (DSF) has been proved good anti-tumor effect and even better with coadministration of Cu. In this work, we report the use of hyaluronic acid (HA) based materials to construct vectors for the delivery of both DSF and Cu. HA was firstly modified with polyethylene glycol monomethyl ether (mPEG) and polycaprolactone (PCL) to synthesize an amphiphilic polymer (HA-PEG-PCL). DSF could be loaded in the hydrophobic core and Cu could be cooperated to the negative hydrophilic segment. The Cu also played a role as crosslinking agent, which prevented DSF leakage prematurely, avoiding the bad side effects to normal tissues. The interaction between HA and CD44 improved the distribution of nanodrugs in tumor cells. When the nanodrugs were delivered to the cancer cell, the acidic micro-environment would separate the Cu from the surface, leading to the disintegration of the micelles, promoting the release of DSF from the micelle core. The results of in vitro and in vivo experiments showed that the DSF and Cu co-delivery vector constructed in this work could enhance the antitumor effect and have low biological toxicity.