Green synthesis of hyaluronic acid-based silver nanoparticles and their enhanced delivery to CD44+ cancer cells

The potent antitumor activities of silver nanoparticles (AgNP) have attracted great attention. However, the application of AgNP is restricted by its non-specific delivery and poor cellular uptake. We developed a novel hyaluronic acid (HA)-based strategy for the green synthesis of AgNP, in which HA was used as the reducing agent and stabilizer. More importantly, HA is a ligand of CD44, and the HA-modified AgNP can target CD44 receptors that are overexpressed in many types of cancer cells. The CD44-dependent endocytosis can significantly increase the intracellular delivery of HA-AgNP, compared to the non-modified one. The antitumor efficacy was significantly improved by HA modification. Furthermore, we found that multiple mechanisms were involved for the enhanced anticancer activities of HA-AgNP, including the decline of mitochondrial membrane potential, cell-cycle arrest, apoptosis, and autophagy. The HA-based strategy for green synthesis and CD44-targeting delivery provided a promising solution for AgNP-mediated cancer treatment.