Dopamine-derived nanoparticles for the protection of irradiation-induced intestinal injury by maintaining intestinal homeostasis
Dopamine-derived nanoparticles for the protection of irradiation-induced intestinal injury by maintaining intestinal homeostasis
复制标题
多巴胺衍生纳米颗粒通过维持肠道稳态来保护辐射引起的肠道损伤
DOI：
10.1039/d1bm02026a
复制
发表时间：
2022-05-12
影响因子：
6.6
通讯作者：
Liu, Jianjun
中科院分区：
文献类型：
--
作者：
Jia, Shuhan;Dong, Suhe;Liu, Jianjun
腹部和盆腔肿瘤的放射治疗几乎不可避免地通过氧化应激损伤肠道并引起炎症。遗憾的是，传统的用于辐射（IR）诱导的肠损伤的辐射防护剂遭受挑战，诸如溶解性差、不令人满意的生物活性和不期望的不良反应，这显著限制了它们的有用性。聚多巴胺纳米粒（PDA-NPs）在清除活性氧（ROS）和抑制炎症方面显示出很好的潜力。本研究采用一种简单的方法制备PDA-NPs，并对其物理性质进行了表征。小鼠间隔22小时通过口服管饲法接受两个剂量的PDA-NP，并在最后一次管饲后2小时用X射线照射。探讨PDA-NPs对IR诱导的肠损伤的保护作用及其可能的机制。结果表明，PDA-NPs呈球形，分散性好，形状均匀，结构致密，胶体分散稳定性好，吸光度与浓度相关，定量准确。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屏障功能。特别是PDA-NPs显著抑制IR后Lgr 5（+）肠干细胞（ISCs）的耗竭，促进细胞再生，表明维持了ISCs的再生能力，促进了肠道结构和功能的修复。PDA-NPs能显著抑制电离辐射诱导的肠细胞凋亡、炎性细胞凋亡和DNA损伤。总之，我们的研究表明PDA-NPs在保护肠道免受电离辐射损伤方面可能具有巨大的潜力。
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.