Mg-Hydroxyapatite Nanorods for Dual Intracellular Doxorubicin Delivery and Osteogenic-Associated BM-MSC Responses

Intracellular drug therapies are based on the use of nanocarriers that can successfully penetrate cell barriers and release therapeutic payloads directly inside the cell environment. In this context, hydroxyapatite (HA) nanoparticles provide a particularly promising platform owing to their inherent biocompatibility, bioactivity, and drug-binding capability. This work hence examines anisotropic HA nanorods (NRs), synthesized using hydrothermal methods, with a particular focus on Mg-to-Ca ion substitution, aiming to increase the bioactivity and improve the interaction with therapeutics, specifically targeting intracellular sustained release. Our findings indicate that increasing the extent of Mg doping in apatite NRs induces enhanced cell compatibility and interaction with primary human bone marrow-derived mesenchymal stem cells. Moreover, the doping with Mg²⁺ enhances the NRs capacity to link and release doxorubicin, a widely used antitumor drug, in human osteosarcoma cells. The enhanced functionality is attributed to the Mg²⁺-induced structural disorder at the NR surface, which reduces the crystallinity and increases the number of reactive surface sites. As a result, Mg²⁺ doping has emerged as a promising strategy for optimizing the functional performance of apatite-based nanocarriers, highlighting their potential applications in nanomedicine and precision medicine.