Synthesis and antitumor activity of ultra-low molecular weight hyaluronic acid-decorated camptothecin conjugates

Camptothecin (CPT) exhibits potent anticancer activity, but its clinical application is limited by poor solubility and severe side effects. Hyaluronic acid (HA) is gaining attention in drug delivery systems due to its excellent biocompatibility and tumor-targeting properties. In this study, we conjugated CPT to the reducing end of ultra-low molecular weight HA to create a series of HA-decorated CPT conjugates. These novel conjugates offer significant advantages over traditional HA-drug formulations, including well-defined structures and consistent drug-loading rates. In vitro studies demonstrated that these HA-decorated conjugates exhibited enhanced anti-proliferative and targeting effects towards various tumor cells. Furthermore, in vivo studies showed that HA-CPT nanoparticles significantly inhibited tumor growth with minimal side effects, as evidenced by stable body weight and histological analyses in treated mice. The approach of using structurally well-defined HA as a carrier for site-specific drug modification expands the potential applications of HA and enhances the therapeutic efficacy of conventional drugs.