Zoledronic acid (ZOL) has been approved as the only
bisphosphonate for the prevention and treatment of metastatic
bone diseases with acceptable safety and tolerability. However, systemic or direct injection of ZOL often causes severe side effects, which limits its clinical application. Here, an innovative
nano-drug delivery system, ZOL-loaded
hyaluronic acid/
polyethylene glycol/nano-
hydroxyapatite nanoparticles (HA-PEG-nHA-ZOL NPs), has been found to effectively inhibit the proliferation of three types of human
osteosarcoma cell lines (143b, HOS, and MG63) at 1-10 μmol/L, while with low cell cytotoxicity on normal cells. The NPs significantly enhanced the apoptosis-related
protein expression and
tumor cell apoptosis rate. The NPs could also inhibit the proliferation of
osteosarcoma cells by blocking the S phase of the cell cycle. In the orthotopic
osteosarcoma nude mice model, local injection of the HA-PEG-nHA-ZOL NPs stimulated
tumor necrosis, apoptosis, and granulocyte infiltration in the blood vessels. Altogether, the ZOL
nano-delivery system possesses great potential for local treatment to prevent local
tumor recurrence and can be applied in clinical
osteosarcoma therapy.