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Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles

Author

Listed:
  • Xufei Bian

    (Southwest University
    Peking University)

  • Ling Yang

    (Southwest University)

  • Dingxi Jiang

    (Southwest University)

  • Adam J. Grippin

    (The University of Texas MD Anderson Cancer Center)

  • Yifan Ma

    (The University of Texas MD Anderson Cancer Center)

  • Shuang Wu

    (Southwest University)

  • Linchong Wu

    (Southwest University)

  • Xiaoyou Wang

    (Southwest University
    Peking University)

  • Zhongjie Tang

    (Southwest University)

  • Kaicheng Tang

    (Southwest University)

  • Weidong Pan

    (Guizhou University)

  • Shiyan Dong

    (The University of Texas MD Anderson Cancer Center)

  • Betty Y. S. Kim

    (The University of Texas MD Anderson Cancer Center)

  • Wen Jiang

    (The University of Texas MD Anderson Cancer Center)

  • Zhaogang Yang

    (Jilin University)

  • Chong Li

    (Southwest University
    Peking University)

Abstract

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.

Suggested Citation

  • Xufei Bian & Ling Yang & Dingxi Jiang & Adam J. Grippin & Yifan Ma & Shuang Wu & Linchong Wu & Xiaoyou Wang & Zhongjie Tang & Kaicheng Tang & Weidong Pan & Shiyan Dong & Betty Y. S. Kim & Wen Jiang & , 2024. "Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48461-4
    DOI: 10.1038/s41467-024-48461-4
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    References listed on IDEAS

    as
    1. Xuexiang Han & Hanwen Zhang & Kamila Butowska & Kelsey L. Swingle & Mohamad-Gabriel Alameh & Drew Weissman & Michael J. Mitchell, 2021. "An ionizable lipid toolbox for RNA delivery," Nature Communications, Nature, vol. 12(1), pages 1-6, December.
    2. Nicholas G. Zaorsky & Ying Zhang & Leila T. Tchelebi & Heath B. Mackley & Vernon M. Chinchilli & Brad E. Zacharia, 2019. "Stroke among cancer patients," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
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