Deep Learning Enhanced Near Infrared-II Imaging and Image-Guided Small Interfering Ribonucleic Acid Therapy of Ischemic Stroke.

Journal: ACS nano
PMID: 40042964

Abstract

Small interfering RNA (siRNA) targeting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as a promising therapeutic strategy to mitigate infarct volume and brain injury following ischemic stroke. However, the clinical translation of siRNA-based therapies is significantly hampered by the formidable blood-brain barrier (BBB), which restricts drug penetration into the central nervous system. To address this challenge, we have developed an innovative long-circulating near-infrared II (NIR-II) nanoparticle platform YWFC NPs, which is meticulously engineered to enhance BBB transcytosis and enable efficient delivery of siRNA targeting NLRP3 (siNLRP3@YWFC NPs) in preclinical models of ischemic stroke. Furthermore, we integrated advanced deep learning neural network algorithms to optimize NIR-II imaging of the cerebral infarct penumbra, achieving an improved signal-to-background ratio at 72 h poststroke. studies employing middle cerebral artery occlusion (MCAO) mouse models demonstrated that image-guided therapy with siNLRP3@YWFC NPs, guided by prolonged NIR-II imaging, resulted in significant therapeutic benefits.

Authors

  • Kai Yu
  • Lidan Fu
    CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, China.
  • Yu Chao
    College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.
  • Xiaodong Zeng
    School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
  • Yonggang Zhang
    Department of Radiology, The First People's Hospital of Lianyungang, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, China.
  • Yuanyuan Chen
    Center for Radiation Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou 310001, China.
  • Jialu Gao
    Department of Neurosurgery, Central Laboratory, Renmin Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
  • Binchun Lu
    Department of Precision Instrument, Tsinghua University, Beijing 100084, China.
  • Hua Zhu
    School of Kinesiology, Shanghai University of Sport Shanghai, China.
  • Lijuan Gu
    Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Xiaoxing Xiong
    Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.
  • Zhenhua Hu
  • Xuechuan Hong
    Department of Neurosurgery, Central Laboratory, Renmin Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
  • Yuling Xiao
    State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.

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