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 × 10−2mmol. 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.
放射治疗是一种广泛应用于癌症治疗与缓解的非侵入性方法。然而，辐射通过增加氧化应激和炎症反应对免疫系统产生的影响与多种副作用相关。因此，为保护此类患者的正常器官及免疫系统免受辐射损伤，开发有效的临床放射防护策略至关重要。为探索毒性更低、更有效的放射防护剂，本研究合成了一种线粒体靶向的三苯基膦离子偶联硝酰基自由基化合物（TPP-NIT），并制备表征了其纳米颗粒（NPs-TPP-NIT）。NPs-TPP-NIT粒径分布窄且分散均匀，表现出良好的药物包封效率和低溶血率（<3%）。通过体外和体内实验评估了NPs-TPP-NIT对X射线辐射诱导氧化损伤的保护作用。结果显示，当浓度低于1.5×10⁻² mmol时，NPs-TPP-NIT对L-02细胞无明显细胞毒性；在2、4、6、8 Gy X射线照射下能显著提高L-02细胞存活率，其中6 Gy照射后小鼠存活率最高。实验还表明，L-02细胞经6.0 Gy X射线照射后，NPs-TPP-NIT能提高超氧化物歧化酶（SOD）活性并降低丙二醛（MDA）水平，同时显著抑制细胞凋亡。NPs-TPP-NIT可显著提升照射后小鼠存活率，并有效缓解辐射引起的红细胞（RBCs）、白细胞（WBCs）和血小板（PLTs）耗竭。这些结果证明了NPs-TPP-NIT用于辐射损伤防护的可行性。综上所述，本研究表明NPs-TPP-NIT有望成为新型放射防护剂，在肿瘤放射治疗中保护健康组织和器官免受辐射损伤。
肿瘤(癌症)患者之家