The Postgraduate Training Base of Jinzhou Medical University (The PLA Rocket Force Characteristic Medical Center), Beijing, China.
The PLA Rocket Force Characteristic Medical Center, Beijing, China.
Biomater Sci. 2022 Jun 14;10(12):3309-3322. doi: 10.1039/d1bm02026a.
Radiotherapy of abdominal and pelvic tumors almost inevitably injures the intestine by oxidative stress and causes inflammation. Regrettably, traditional radioprotective agents for irradiation (IR) induced intestinal injury suffer from challenges such as poor solubility, unsatisfactory bioactivity and undesired adverse reactions, which significantly limit their usefulness. Polydopamine nanoparticles (PDA-NPs) have shown promising potential in scavenging reactive oxygen species (ROS) and suppressing inflammation. In this study, PDA-NPs were prepared by a simple method and their physical properties were characterized. Mice received two doses of PDA-NPs by oral gavage 22 h apart, and were irradiated with X-rays 2 h after the last gavage. The protective effect of PDA-NPs and possible mechanisms of protection against IR-induced intestinal injury were explored. The results showed that PDA-NPs were spherical and well dispersed, with good shape uniformity, compact structure, good colloid dispersion stability, concentration-dependent light absorption, and accurate quantification. Importantly, PDA-NPs reduced mortality and prolonged the average survival time of mice after IR. Furthermore, PDA-NPs protected mice from IR-induced injury to crypt-villus units and maintained intestinal barrier function in the intestine. In particular, PDA-NPs significantly inhibited the depletion of Lgr5 intestinal stem cells (ISCs) and promoted cell regeneration after IR, which indicated that the regeneration ability of ISCs was maintained and the repair of intestinal structure and function was promoted. Finally, PDA-NPs significantly suppressed the apoptosis, inflammatory pyroptosis and DNA damage of intestinal cells induced by ionizing radiation. Altogether, our study suggested that PDA-NPs may have great potential in protecting the intestines from ionizing radiation damage.
腹部和盆腔肿瘤的放射治疗几乎不可避免地会通过氧化应激损伤肠道，并引起炎症。遗憾的是，传统的放射防护剂（IR）诱导的肠道损伤存在溶解度差、生物活性不理想和不良反应不理想等问题，这极大地限制了它们的应用。聚多巴胺纳米粒子（PDA-NPs）在清除活性氧（ROS）和抑制炎症方面显示出了有前途的潜力。在这项研究中，通过一种简单的方法制备了 PDA-NPs，并对其物理性质进行了表征。小鼠通过口服灌胃在 22 小时内接受两次 PDA-NPs 剂量，最后一次灌胃后 2 小时用 X 射线照射。研究了 PDA-NPs 的保护作用及其对 IR 诱导的肠道损伤的可能保护机制。结果表明，PDA-NPs 呈球形且分散良好，具有良好的形状均匀性、紧凑的结构、良好的胶体分散稳定性、浓度依赖性光吸收和准确的定量。重要的是，PDA-NPs 降低了 IR 后小鼠的死亡率并延长了平均存活时间。此外，PDA-NPs 保护小鼠免受 IR 诱导的隐窝绒毛单位损伤，并维持肠道内的肠道屏障功能。特别是，PDA-NPs 显著抑制了 Lgr5 肠干细胞（ISCs）在 IR 后的耗竭，并促进了细胞再生，这表明 ISCs 的再生能力得到维持，促进了肠道结构和功能的修复。最后，PDA-NPs 显著抑制了电离辐射诱导的肠细胞凋亡、炎症性细胞焦亡和 DNA 损伤。总之，我们的研究表明 PDA-NPs 可能在保护肠道免受电离辐射损伤方面具有很大的潜力。
