Novel Reductive Responsive Chrysin-Oligomeric Hyaluronic Acid Nanomaterials to Curcumin Delivery for Cancer Therapy

Drug resistance, perplexing a lot of doctors and patients, was an inevitable challenge in the field of effective cancer therapy. Poor water solubility, inefficient aggregation at tumor site and killing normal cells were also the great obstacles, which gave rise to failure in the tumor clinical treatment. In order to overcome these difficulties, modified targeting nano-micelles (MT-NMs) loading Curcumin (Cur) and Chrysin (Chr) were designed. In this work, dithiodipropionic acid (DA), a reduction-sensitive material, acted as a "messenger" linker connecting Chr and oligomeric hyaluronic acid (oHA). Then, the amphiphilic polymer, oligomeric hyaluronic acid-dithiodipropionic acid-Chrysin (oHA-DA-Chr), was synthesized. What's more, combinational therapy is a better way to cripple cancer drug-resistant and reinforce the therapeutic efficacy. In this study, 1H-NMR was used to authenticate the structure of oHA-DA-Chr. The amphiphilic oHA-DA-Chr could self-assemble into nano-micelles (NMs) in water. The NMs with small size (223.2±2.4 nm) could concentrate well at tumor sites by enhancing permeability and retention effect (EPR) and CD44 receptor targeting property of oHA. The Cur could release well from NMs when disulfide bond (S–S) of DA was exposed to tumor environment containing high concentration of glutathione (GSH).