Biomimetic Citrate-Coated Luminescent Apatite Nanoplatforms for Diclofenac Delivery in Inflammatory Environments

This research was funded by Spanish Agencia Estatal de Investigacion (AEI) of the Ministerio de Ciencia e Innovacion (MCI) and co-funded with FEDER, UE, Project No. PGC2018-102047-B-I00 (MCIU/AEI/FEDER, UE). M.P. acknowledges the Progetto di Ricerca Fondi di Ateneo per la Ricerca-FAR 2018 "Development of innovative biological materials for the functional regeneration of cardiac tissue models".Luminescent nanoparticles are innovative tools for medicine, allowing the imaging of cells and tissues, and, at the same time, carrying and releasing different types of molecules. We explored and compared the loading/release ability of diclofenac (COX-2 antagonist), in both undoped- and luminescent Terbium(3+) (Tb3+)-doped citrate-coated carbonated apatite nanoparticles at different temperatures (25, 37, 40 degrees C) and pHs (7.4, 5.2). The cytocompatibility was evaluated on two osteosarcoma cell lines and primary human osteoblasts. Biological effects of diclofenac-loaded-nanoparticles were monitored in an in vitro osteoblast's cytokine-induced inflammation model by evaluating COX-2 mRNA expression and production of PGE(2). Adsorption isotherms fitted the multilayer Langmuir-Freundlich model. The maximum adsorbed amounts at 37 degrees C were higher than at 25 degrees C, and particularly when using the Tb3+ -doped particles. Diclofenac-release efficiencies were higher at pH 5.2, a condition simulating a local inflammation. The luminescence properties of diclofenac-loaded Tb3+ -doped particles were affected by pH, being the relative luminescence intensity higher at pH 5.2 and the luminescence lifetime higher at pH 7.4, but not influenced either by the temperature or by the diclofenac-loaded amount. Both undoped and Tb3+-doped nanoparticles were cytocompatible. In addition, diclofenac release increased COX-2 mRNA expression and decreased PGE(2) production in an in vitro inflammation model. These findings evidence the potential of these nanoparticles for osteo-localized delivery of anti-inflammatory drugs and the possibility to localize the inflammation, characterized by a decrease in pH, by changes in luminescence.Spanish Agencia Estatal de Investigacion (AEI) of the Ministerio de Ciencia e Innovacion (MCI)European Commission PGC2018-102047-B-I0