Biological Evaluation of Hydroxyapatite Zirconium Nanoparticle as a Potential Radiosensitizer for Lung Cancer X-ray Induced Photodynamic Therapy

Abstract

Photodynamic therapy has been recognized as a viable approach for lung cancer treatment. Some photosensitizer agents are known as X-ray sensitive and could improve radiotherapy efficacy. The use of nanoparticles for drug delivery and as photosensitizer agents offers various advantages because of their rapid cellular accumulation and distribution into target organs. On the other hand, several nanoparticles could trigger adverse effects during cancer treatment. In this article, the biological study of hydroxyapatite zirconium nanoparticles (HApZr) as photosensitizer candidates for X-ray-induced photodynamic therapy has been demonstrated in vitro and in vivo. This nanoparticle increased the intracellular reactive oxygen species (ROS) levels after the delivery of ionizing radiation at 5 Gy to a cancer cell line and showed higher cytotoxicity compared to non-irradiated treatment. In vitro cellular uptake based on cell imaging also indicated a promising intake and an ability to kill cancer cells. Subsequently, an in vivo evaluation using orthotopic lung cancer mouse models also showed their good accumulation in target organs, with lower accumulation in normal lung tissue. Moreover, studies of acute toxicity showed that a dose of 50 μg/mL yielded minor pathological changes on histological evaluations, which were supported by a biochemical analysis. In addition, HApZr nanoparticles also increase TNF-α which enhancing the cytotoxic effect after irradiation. Finally, these findings were important for further investigation of the clinical application of these HApZr nanoparticles for the treatment of patients with lung cancer.