Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China.
Int J Nanomedicine. 2022 Mar 10;17:1005-1014. doi: 10.2147/IJN.S342008. eCollection 2022.
Radiotherapy is a conventional treatment for gastrointestinal tumors. However, its therapeutic effect might not be satisfactory because of factors such as radio-resistance of tumor cells and dose reduction applied to avoid damage to normal tissues. We developed a novel combination therapy involving the use of isoniazid (INH) and core-shell magnetic nanospheres (NPs) to enhance the efficacy of radiotherapy.
Magnetic core-shell NPs were synthesized. The shell manganese dioxide (MnO) reacted with intracellular glutathione to produce Mn, which decomposed hydrogen peroxide (HO) to hydroxyl radicals (·OH) in the presence of INH to produce sufficient amount of reactive oxygen species. In addition to this chemodynamic therapy, MnO catalyzed HO to O, which alleviated hypoxia in tumors and thus enhanced the effect of radiotherapy. In addition, iron oxide (FeO) and reduced Mn were potential candidates for T-T dual-mode magnetic resonance imaging (MRI) with remarkable magnetic targeting ability.
NPs exhibited efficient tumor targeting performance under the magnetic field and improved T/T dual-mode MRI, which elevated oxygen levels without toxicity to the mice to achieve remarkable therapeutic outcomes, reaching a tumor inhibition rate of 93.2%. Moreover, chemodynamic therapy mediated by INH and NPs enhanced the therapeutic effect of radiotherapy both in vivo and in vitro.
The results demonstrated that the combination of INH and NPs could be a novel strategy for radiosensitization with clinical potential.
放射治疗是胃肠道肿瘤的常规治疗方法。然而，由于肿瘤细胞的放射抗性和为避免正常组织损伤而进行的剂量减少等因素，其治疗效果可能并不理想。我们开发了一种新的联合治疗方法，涉及使用异烟肼（INH）和核壳磁性纳米球（NPs）来提高放射治疗的疗效。
合成了磁性核壳 NPs。壳层二氧化锰（MnO）与细胞内谷胱甘肽反应生成 Mn，在 INH 的存在下，Mn 将过氧化氢（HO）分解为羟基自由基（·OH），从而产生足够的活性氧。除了这种化学动力学疗法外，MnO 还催化 HO 生成 O，缓解了肿瘤中的缺氧，从而增强了放射治疗的效果。此外，氧化铁（FeO）和还原 Mn 是 T-T 双模式磁共振成像（MRI）的潜在候选物，具有显著的磁靶向能力。
NPs 在磁场下表现出高效的肿瘤靶向性能，并改善了 T/T 双模式 MRI，提高了氧水平而没有毒性，从而实现了显著的治疗效果，肿瘤抑制率达到 93.2%。此外，INH 和 NPs 介导的化学动力学疗法增强了放射治疗的体内和体外治疗效果。
结果表明，INH 和 NPs 的联合使用可能是一种具有临床潜力的放射增敏新策略。
