Multifunctional hydroxyapatite with potential for application in theranostic nanomedicine

Although several materials are being studied for the development of theranostic systems, factors such as high costs, low yield, stability of nanoparticles (NPs) and toxicity-related issues hinder their application in medicine. Thus, this paper introduces the synthesis of a theranostic system composed of hydroxyapatite (HAp) functionalized with europium (Eu³⁺) and zinc oxide (ZnO) NPs, resulting in a low-cost material that presents biocompatibility, luminescence, antibacterial activity and whose synthesis method is simple. The Eu³⁺ - doped HAp was obtained through the precipitation method and the functionalization with ZnO occurred in the subsequent stage through the solid-state reaction method. The resulting material, [Ca_9.5Eu_0.5(PO₄)₆(OH)₂@ZnO], was characterized by several techniques where the photoluminescence spectrum exhibited sharp peaks at the 4f^N → 4f^N transitions typical of Eu³⁺ ions, while tests with bacteria proved its antibacterial property. The crystal structure obtained by X-ray diffraction confirmed HAp as the major phase. The multifunctional HAp (HAp:Eu@ZnO) was considered as hemocompatible, exhibiting an in vitro hemolysis ratio of 1.85 (±0.2) %, and its loading potential, tested for two antitumor drugs, showed an adsorption capacity of 43.0 ± 3.6% for 5-Fluorouracil and 84.0 ± 4.0% for curcumin. The cytotoxicity of the system as well as its use as a support for drugs was analyzed through in vitro assays with tumor cells from sarcoma 180 in mice. The results confirmed that HAp:Eu@ZnO is non-toxic to cells and its potential for antineoplastic vectorization is increased by cell internalization due to endocytosis, with up to 39.0% of cancer cell deaths having been observed at the concentrations and period evaluated.

Keywords: Antibacterial hydroxyapatite; Photoluminescent hydroxyapatite; Theranostic system.