Specifically Breaking Through the Injured Blood-Brain Barrier With Tannic Acid-Based Nanomedicine for Ischemic Stroke Ischemia Reperfusion Treatment

Xiaojing Shi; Shuya Wang; Tingli Xiong; Ruishi Li; Wenxuan Zheng; Wensheng Chen; Tianjiao Zhao; Yongqi Yang; Xiaohong Ying; Weimin Qi; Yingci Xia; Jue Wang; Yuqi Zhang; Qiong Huang; Yayun Nan; Kelong Ai

doi:10.1002/EXP.20240388

Exploration ›› 2025, Vol. 5 ›› Issue (5) :20240388 DOI: 10.1002/EXP.20240388

RESEARCH ARTICLE

Specifically Breaking Through the Injured Blood-Brain Barrier With Tannic Acid-Based Nanomedicine for Ischemic Stroke Ischemia Reperfusion Treatment

Xiaojing Shi ¹^,²^,³
, Shuya Wang ¹^,²
, Tingli Xiong ¹^,²
, Ruishi Li ¹^,²
, Wenxuan Zheng ¹^,²
, Wensheng Chen ¹^,³
, Tianjiao Zhao ¹^,²
, Yongqi Yang ¹^,²
, Xiaohong Ying ¹^,²
, Weimin Qi ¹^,²
, Yingci Xia ¹^,²
, Jue Wang ¹^,²
, Yuqi Zhang ⁴
, Qiong Huang ¹^,³
, Yayun Nan ⁵
, Kelong Ai ²^,⁶^,⁷^,⁸

Author information +

¹. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China

². Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China

³. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China

⁴. Communication Design, Royal Melbourne Institute of Technology University, Melbourne, Victoria, Australia

⁵. Geriatric Medical Center, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia, China

⁶. Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China

⁷. Key Laboratory of Aging-Related Bone and Joint Diseases Prevention and Treatment, Ministry of Education, Xiangya Hospital, Central South University, Changsha, China

⁸. FuRong Laboratory, Changsha, Hunan, China

qionghuang@csu.edu.cn

nanyy_2009@163.com

aikelong@csu.edu.cn

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Abstract

Protecting neuronal mitochondria by eliminating the mitochondrial ROS (mtROS) storm is crucial to abrogate the neuronal damage cascade of ischemic stroke ischemia reperfusion (ISIR), which is a long-standing challenge in the field of ischemic stroke (IS). Existing blood-brain barrier (BBB) penetration methods are usually unable to distinguish between healthy brain tissue and cerebral infarction tissue, and BBB targeting is not compatible with mitochondrial targeting, resulting in a huge barrier to the specific elimination of mtROS in neuronal mitochondria in ISIR. This study introduces an elegantly designed tannic acid, polydopamine, and Mo-based heteropolyacid ternary composite nanomedicine (TPM), which not only has a superb ability to eliminate multiple ROS thanks to the introduction of polydopamine, but also can actively recognize the injured BBB site, specifically enter the neurons in the cerebral infarction area, and then highly specifically target the mitochondria of neurons to efficiently eliminate mtROS. TPM could significantly inhibit neuronal apoptosis by protecting mitochondria and eliminate inflammation by inhibiting activation of the STING pathway, thereby significantly reducing the size of cerebral infarction. This sequential targeting of TPM from the injured BBB to neuronal mitochondria provides a promising strategy to treat ISIR in the clinical setting.

Keywords

endoplasmic reticulum stress / inflammation / ischemic stroke ischemia reperfusion / mitochondrial targeting / oxidative stress

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Xiaojing Shi, Shuya Wang, Tingli Xiong, Ruishi Li, Wenxuan Zheng, Wensheng Chen, Tianjiao Zhao, Yongqi Yang, Xiaohong Ying, Weimin Qi, Yingci Xia, Jue Wang, Yuqi Zhang, Qiong Huang, Yayun Nan, Kelong Ai. Specifically Breaking Through the Injured Blood-Brain Barrier With Tannic Acid-Based Nanomedicine for Ischemic Stroke Ischemia Reperfusion Treatment. Exploration, 2025, 5(5): 20240388 DOI:10.1002/EXP.20240388

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