Fabrication of bone-targeting hyaluronic acid coupled alendronate-bioactive glass for osteosarcoma therapy

Abstract

Osteosarcoma is a complicated clinical cancer for patients, which seriously reduces the quality of life. The current conventional treatment is focused on controlling cancer cell proliferation and osteoclast activity. The aim is to develop mesoporous bioactive glass (MBG) with bone-targeting hyaluronic acid-alendronate (HA-ALN) components for osteosarcoma treatment. The prepared MBG was enclosed by the HA-ALN to form mesoporous bioactive glass nanocomposites (MBGNCs) and characterized surface functionalization, size, shape, and morphology. MBG nanoparticles were spherical and smooth surfaces; after coating with HA-ALN they exhibited a stable structure with changes in the surface textures. Bisphosphonate coupled HA controls the swelling under physiological conditions by preventing rapid degradation of the nanocomposites. It also confirms the drug release, which shows a maximum of 65% DOX release at pH 4.5. Drug release studies confirm the pH variation was slightly altered in the DOX release ratio due to the HA-ALN. It also helps in higher binding ability on the hydroxyapatite components, indicating the bone targeting ability and nanocomposites. ALN components actively inhibit osteoclast-like cells. MBGNCs witnessed the higher toxicity to the osteosarcoma cancer cells of IC50 value of 4 μg/mL. MBGNCs inhibitory effects on the viability of the MG-63 osteosarcoma cancer cells were higher compared to free DOX. The bone targeting effect of HA-ALN coated MBGNCs shows higher cellular uptake, which helps inhibit tumor growth and helps in the long term of bone tissue regeneration. MBGNCs highly followed the bone targeting, pH-dependent drug release contributed to the treatment of bone metastasis and promoted osteoblast differentiation.