Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles
Year: 2024
Type: article
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.
Source: Nature Communications
Authors: 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, Zhaogang Yang, Chong Li
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: National Natural Science Foundation of China, Chongqing University, Centre Scientifique et Technique du Bâtiment, University of Texas MD Anderson Cancer Center, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, National Cancer Institute
OpenAlex ID: W4396833902