Synthesis and Characterization of Oleic Acid-Coated Calcium Phosphate Nanoparticles for Gene Delivery Applications

Background: Efficient gene delivery remains a major challenge in gene therapy, necessitating the development of biocompatible and effective carrier systems. This study aimed to synthesize and evaluate oleic acid-modified calcium phosphate (OA-CaP) nanoparticles for their potential as a non-viral gene delivery vector. Methods: Oleic acid-modified calcium phosphate nanoparticles were synthesized and characterized using dynamic light scattering (DLS), zeta potential analysis, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and transfection efficiency was evaluated in L929 cells using fluorescence microscopy. Phase-contrast microscopy was used to observe cell morphology and proliferation. Results: Oleic acid-modified calcium phosphate nanoparticles exhibited a smaller size (193.1 ± 12.7 nm) and a higher surface charge (+22.6 ± 2.7 mV) compared to unmodified CaP, resulting in improved colloidal stability and cellular interactions. Cytotoxicity analysis indicated high cell viability at lower concentrations, while a dose-dependent decrease in viability was observed at higher concentrations. Transfection studies demonstrated significantly higher gene expression in OA-CaP/pDNA-transfected cells compared to naked pDNA. Transfection efficiencies increased from 22.24% ± 20.13% at 24 hours to 72.43% ± 36.57% at 72 hours. Additionally, phase-contrast microscopy confirmed maintained cell morphology and enhanced proliferation. Conclusion: Oleic acid-modified calcium phosphate nanoparticles exhibit high transfection efficiency and minimal cytotoxicity at optimized concentrations, highlighting their potential as a promising gene delivery system. Future studies should focus on in vivo evaluations to further establish their therapeutic applicability in gene therapy. Cite this article as: Akkurt Yıldırım, M. Synthesis and characterization of oleic acid-coated calcium phosphate nanoparticles for gene delivery applications. Trends in Pharmacy, 2025, 2, 0002, doi: 10.5152/TrendsPharm.2025.25002.