Facile synthesis of metformin loaded Mn₃O₄-HAp magnetic hydroxyapatite nanocomposites for T₁-magnetic resonance imaging guided targeted chemo-phototherapy in vitro

Magnetic hydroxyapatite nanocomposites are promising candidates for various biomedical applications. However, the uncontrolled growth with the unfavorable size limits their widespread utilization in real-time applications. Herein, a facile method was utilized to fabricate uniform spherical-shaped nanocomposites of manganese oxide combined hydroxyapatite (Mn₃O₄-HAp) with an average size of about 28 nm. The structural characterization reveals the presence of Mn₃O₄ in the crystalline phase, confined by HAp to give a composite structure. The biocompatibility and drug loading capability of Mn₃O₄-HAp nanocomposites are improved by surface modification using Food and Drug Administration-approved triblock copolymer Pluronic® F-127, followed by folic acid (FA) for targeting ability. Taking advantage of the surface properties of the polymer and the drug delivery potential of HAp, metformin was encapsulated in the prepared nanocomposites with a loading capacity of 98 %. The prepared nanocomposites indicate promising cell viability up to 87 % and an excellent drug release profile in an acidic atmosphere. Moreover, the magnetic component Mn₃O₄ presents auspicious T₁-Magnetic resonance imaging with notable r₁ relaxivity of 2.166 mM⁻¹s⁻¹. Further, the Mn₃O₄-HAp@PF127-FA-drug nanocomposites demonstrate good cellular uptake and excellent reactive oxygen species (ROS) production under low-intensity UV irradiation, resulting in a remarkable photodynamic therapeutic effect. The results showed that the designed Mn₃O₄-HAp nanocomposites are promising targeted chemo-theranostic agents.