Mitochondria-Targeted Nitronyl Nitroxide Radical Nanoparticles for Protection against Radiation-Induced Damage with Antioxidant Effects

Shigao Huang; Min Xu; Qingyue Da; Linlin Jing; Haibo Wang

doi:10.3390/cancers16020351

Mitochondria-Targeted Nitronyl Nitroxide Radical Nanoparticles for Protection against Radiation-Induced Damage with Antioxidant Effects

Cancers (Basel). 2024 Jan 13;16(2):351. doi: 10.3390/cancers16020351.

Authors

Shigao Huang^{1

2}, Min Xu³, Qingyue Da⁴, Linlin Jing⁴, Haibo Wang³

Affiliations

¹ Department of Cell Biology, National Translational Science Center for Molecular Medicine, The Air Force Medical University, Xi'an 710032, China.
² Department of Radiation Oncology, Xijing Hospital, The Air Force Medical University, Xi'an 710032, China.
³ Department of Chemistry, School of Pharmacy, The Air Force Medical University, Xi'an 710032, China.
⁴ Centre for Translational Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.

Abstract

Radiotherapy is a non-invasive method that is widely applied to treat and alleviate cancers. However, radiation-induced effects in the immune system are associated with several side effects via an increase in oxidative stress and the inflammatory response. Therefore, it is imperative to develop effective clinical radiological protection strategies for the radiological protection of the normal organs and immune system in these patients. To explore more effective radioprotective agents with minimal toxicity, a mitochondria-targeted nitronyl nitroxide radical with a triphenylphosphine ion (TPP-NIT) was synthesized and its nanoparticles (NPs-TPP-NIT) were prepared and characterized. The TPP-NIT nanoparticles (NPs-TPP-NIT) were narrow in their size distribution and uniformly distributed; they showed good drug encapsulation efficiency and a low hemolysis rate (<3%). The protective effect of NPs-TPP-NIT against X-ray irradiation-induced oxidative damage was measured in vitro and in vivo. The results show that NPs-TPP-NIT were associated with no obvious cytotoxicity to L-02 cells when the concentration was below 1.5 × 10^-2 mmol. NPs-TPP-NIT enhanced the survival rate of L-02 cells significantly under 2, 4, 6, and 8 Gy X-ray radiation exposure; the survival rate of mice was highest after 6 Gy X-ray irradiation. The results also show that NPs-TPP-NIT could increase superoxide dismutase (SOD) activity and decrease malondialdehyde (MDA) levels after the L-02 cells were exposed to 6.0 Gy of X-ray radiation. Moreover, NPs-TPP-NIT could significantly inhibit cell apoptosis. NPs-TPP-NIT significantly increased the mouse survival rate after irradiation. NPs-TPP-NIT displayed a marked ability to reduce the irradiation-induced depletion of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). These results demonstrate the feasibility of using NPs-TPP-NIT to provide protection from radiation-induced damage. In conclusion, this study revealed that NPs-TPP-NIT may be promising radioprotectors and could therefore be applied to protect healthy tissues and organs from radiation during the treatment of cancer with radiotherapy.

Keywords: ionizing radiation; mitochondria-targeted; nitronyl nitroxide radical; radioprotective effect; tumor radiotherapy.

Abstract

Grants and funding