Synthesis and characterization of hyaluronic acid–platinum(iv) nanoconjugate with enhanced antitumor response and reduced adverse effects
A hyaluronic acid–platinum(IV) nanoconjugate with a high drug loading capacity was developed to mitigate the side effects of platinum(II). Pt(IV), HA–EDA, and HA–EDA–Pt(IV) nanoconjugates were investigated by 1H NMR, 13C NMR, FT-NIR, and DSC. Negatively charged polymer–drug conjugates were of a uniform size around 186.4 nm and spherical in shape. In vitro antiproliferation and in vivo apoptosis assays proved that the nanomedicine possessed high cytotoxicity towards cancer cells. The enhanced antitumor effect was attributed to HA receptor-mediated endocytosis. Nanoscale conjugates exhibited desirable blood compatibility and negligible stimulation to blood vessels. The systemic toxicity study showed that polymer–drug conjugates were much safer than the parent drug evidenced by biochemical and histological analyses. The concise design of the nanoconjugate offers a simple way to overcome the toxicity and non-selectivity of cisplatin, which could improve therapeutical outcomes of platinum drugs in cancer therapy.