Chemical bonding of Epigallocatechin-3-gallate to the surface of nano-hydroxyapatite to enhance its biological activity for anti-osteosarcoma

Post-surgical defect repair combined with the elimination of residual cancer cells remains a major clinical challenge for the therapy of malignant bone tumors. As a natural product extracted from green tea, epigallocatechin-3-gallate (EGCG) has a wide range of biological activities. In this study, we investigated the anti-osteosarcoma and osteogenic potential of the natural compound EGCG in combination with hydroxyapatite (HA) for the post-operative treatment of osteosarcoma. We have synthesized well-dispersed surface amino-functionalized hydroxyapatite nanoparticles by the template method combined with surface modification techniques. Then, we conjugated EGCG with HA nanoparticles via amido linkage to prevent burst release of the biomolecules and improve their stability. The results showed that the as-prepared HA-EGCG nanoparticles had the same antioxidant activity as pure EGCG. The HA-EGCG nanoparticles demonstrated efficient EGCG release upon enzyme interactions in an acidic tumor environment, facilitating the accumulation of EGCG in tumor tissues and improving its bioavailability. Compared with pure EGCG and HA, HA-EGCG exhibited enhanced anticancer activity in vitro and in vivo. Furthermore, HA-EGCG could effectively promote osteogenic differentiation. This covalent strategy provides a simple method to fabricate a pH and enzyme-mediated delivery platform to refine the stability and bioavailability of EGCG. This research provides a strategy into designing biomaterials combined with EGCG for the potential application in bone diseases.