Departments of Internal Medicine, Chonnam National University Medical School, 160, Baekseo‑ro, Dong‑gu, Gwangju, 61469, Republic of Korea.
Departments of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea.
J Nanobiotechnology. 2022 Apr 27;20(1):205. doi: 10.1186/s12951-022-01410-z.
The reactive oxygen species (ROS) and inflammation, a critical contributor to tissue damage, is well-known to be associated with various disease. The kidney is susceptible to hypoxia and vulnerable to ROS. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of chronic kidney disease and finally, end-stage renal disease. Thus, delivering therapeutic agents to the ROS-rich inflammation site and releasing the therapeutic agents is a feasible solution.
We developed a longer-circulating, inflammation-sensing, ROS-scavenging versatile nanoplatform by stably loading catalase-mimicking 1-dodecanethiol stabilized MnO (dMnO) nanoparticles inside ROS-sensitive nanomicelles (PTC), resulting in an ROS-sensitive nanozyme (PTC-M). Hydrophobic dMnO nanoparticles were loaded inside PTC micelles to prevent premature release during circulation and act as a therapeutic agent by ROS-responsive release of loaded dMnO once it reached the inflammation site.
The findings of our study demonstrated the successful attenuation of inflammation and apoptosis in the IRI mice kidneys, suggesting that PTC-M nanozyme could possess promising potential in AKI therapy. This study paves the way for high-performance ROS depletion in treating various inflammation-related diseases.
活性氧（ROS）和炎症是导致组织损伤的关键因素，众所周知，它们与各种疾病有关。肾脏容易受到缺氧和 ROS 的影响。因此，氧化应激和肾脏缺氧之间的恶性循环对慢性肾病的进展至关重要，最终导致终末期肾病。因此，将治疗剂递送到富含 ROS 的炎症部位并释放治疗剂是一种可行的解决方案。
我们通过将模拟过氧化氢酶的 1-十二硫醇稳定的 MnO（dMnO）纳米颗粒稳定装载在 ROS 敏感的纳米胶束（PTC）内，开发了一种循环时间更长、炎症感应、ROS 清除的多功能纳米平台，从而产生了一种 ROS 敏感的纳米酶（PTC-M）。疏水性的 dMnO 纳米颗粒被装载在 PTC 胶束内，以防止在循环过程中过早释放，并在到达炎症部位时通过 ROS 响应性释放负载的 dMnO 发挥治疗作用。
本研究结果表明，PTC-M 纳米酶成功减轻了 IRI 小鼠肾脏的炎症和细胞凋亡，这表明 PTC-M 纳米酶在 AKI 治疗中具有很大的潜力。本研究为治疗各种炎症相关疾病提供了高效的 ROS 耗竭方法。
