Sun Tuanwei, Jiang Dawei, Rosenkrans Zachary T, Ehlerding Emily B, Ni Dalong, Qi Chao, Kutyreff Christopher J, Barnhart Todd E, Engle Jonathan W, Huang Peng, Cai Weibo
Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, P. R. China.
Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States.
Adv Funct Mater. 2019 Nov 28;29(48). doi: 10.1002/adfm.201904833. Epub 2019 Sep 25.
Acute kidney injury (AKI) is frequently associated with oxidative stress and causes high mortality annually in clinics. Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for the treatment of AKI. Herein, a novel biomedical use of the endogenous biopolymer melanin as a theranostic natural antioxidant defense nanoplatform for AKI is reported. In this study, ultrasmall Mn-chelated melanin (MMP) nanoparticles are easily prepared via a simple coordination and self-assembly strategy, and further incorporated with polyethylene glycol (MMPP). experiments reveal the ability of MMPP nanoparticles to scavenge multiple toxic reactive oxygen species (ROS) and suppress ROS-induced oxidative stress. Additionally, results from a murine AKI model demonstrate preferential renal uptake of MMPP nanoparticles and a subsequent robust antioxidative response with negligible side effects according to positron emission tomography/magnetic resonance (PET/MR) bimodal imaging and treatment assessment. These results indicate that the effectiveness of MMPP nanoparticles for treating AKI suggests the potential efficacy of melanin as a natural theranostic antioxidant nanoplatform for AKI, as well as other ROS-related diseases.
急性肾损伤（AKI）常与氧化应激相关，每年在临床上导致高死亡率。纳米技术介导的抗氧化治疗正在成为治疗AKI的一种新策略。在此，报道了内源性生物聚合物黑色素作为AKI的治疗诊断天然抗氧化防御纳米平台的一种新的生物医学用途。在本研究中，通过简单的配位和自组装策略轻松制备了超小的锰螯合黑色素（MMP）纳米颗粒，并进一步与聚乙二醇结合（MMPP）。实验揭示了MMPP纳米颗粒清除多种有毒活性氧（ROS）并抑制ROS诱导的氧化应激的能力。此外，根据正电子发射断层扫描/磁共振（PET/MR）双峰成像和治疗评估，小鼠AKI模型的结果表明MMPP纳米颗粒优先被肾脏摄取，随后产生强大的抗氧化反应且副作用可忽略不计。这些结果表明，MMPP纳米颗粒治疗AKI的有效性表明黑色素作为AKI以及其他与ROS相关疾病的天然治疗诊断抗氧化纳米平台具有潜在疗效。
