Adv. Funct. Mater.: Minocycline-Loaded Cerium Oxide Nanoparticles for the Enhanced Treatment of Intracerebral Hemorrhage

Title：

Minocycline-Loaded Cerium Oxide Nanoparticles for the Enhanced Treatment of Intracerebral Hemorrhage

Authors：

Xiang Xu^1#, Zhihui Han^2#, Dong Li^1,3#, Xingshun Xu^4,5, Yaobo Liu⁵, Cong Cao⁵, Jin Tao^5,6, Jian Cheng⁶, John H Zhang⁷, Liang Cheng²* & Gang Chen¹*

Institutions：

¹Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

²Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.

³Department of Neurosurgery, Lianyungang TCM Hospital, Affiliated to Nanjing University of Chinese Medicine, Liangyungang 222000, China.

⁴Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

⁵Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China.

⁶Department of Physiology and Neurobiology, Medical College of Soochow University, Suzhou 215123, China.

⁷Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.

Abstract：

Inflammatory responses and neuronal ferroptosis, which are associated with abnormal accumulation of reactive oxygen species (ROS), exert crucial damaging effects on the brain after intracerebral hemorrhage (ICH). In this study, minocycline (MC)‐loaded cerium oxide nanoparticles (CeO₂‐MC) are constructed for combined ICH treatment. Ultra-small CeO₂(≈5 nm) synthesized via a high-temperature approach exhibits powerful free‐radical scavenging and iron‐chelating abilities. In vitro experiments demonstrated that CeO₂‐MC effectively attenuated the ROS levels in mouse microglial cells and neurons following oxyhemoglobin stimulation. In addition, CeO₂‐MC exhibits iron chelation properties and stabilizes the mitochondrial membrane potential, thereby promoting anti-inflammatory responses and preventing neuronal ferroptosis. In an intracerebral hemorrhage (ICH) mouse model, CeO₂-MC exhibited robust free radical scavenging capabilities and demonstrated the ability to preserve mitochondrial morphology and function, mitigate brain edema, and maintain blood-brain barrier integrity by inhibiting neuroinflammation and ferroptosis. Neurobehavioral tests demonstrated that CeO₂‐MC significantly ameliorated spatial learning ability and sensorimotor function after ICH. Consequently, a general strategy using CeO₂nanoparticles to augment the therapeutic efficacy of MC highlights a new perspective for the in‐depth treatment of ICH.

IF：

18.5

Link：

https://doi.org/10.1002/adfm.202313198

Editor: Guo Jia