Therapeutic carrier based on solanesol and hyaluronate for synergistic tumor treatment

The administration of nanodrugs can lead to metabolism related systemic toxicity due to the use of inert carriers in large quantities. Carrier materials that offer therapeutic effects are therefore a promising means of addressing this limitation. Herein, a hyaluronate-based nanocarrier was prepared from hyaluronic acid (HA) and solanesol. Solanesyl thiosalicylate (STS) derived from solanesol has certain antitumor effects and was used to modify HA. The conjugate (HA-STS) self-assembled into nanoparticles acting as a drug carrier. The synthesis of the conjugates was confirmed by ¹H NMR spectroscopy. Doxorubicin (DOX) was loaded into the HA-STS nanoparticles with a relatively high content of 6.0%. pH-sensitive drug release behavior was achieved by introducing a hydroazone bond between STS and HA. A cytotoxicity assay indicated that the blank nanoparticles had an antitumor effect, which was enhanced by loading with an additional drug. Moreover, in vivo antitumor experiments indicated that the HA-STS-DOX showed superior tumor inhibition compared with free DOX, as well as lower cardiotoxicity and hepatotoxicity, demonstrating the advantages of the bioactive drug vehicles in cancer therapy.