title: Multimodal nanoprobes evaluating physiological pore size of brain vasculatures in ischemic stroke models.
abstract: Ischemic stroke accounts for 80% strokes and originates from a reduction of cerebral blood flow (CBF) after vascular occlusion. For treatment, the first action is to restore CBF by thrombolytic agent recombinant tissue-type plasminogen activator (rt-PA). Although rt-PA benefits clinical outcome, its application is limited by short therapeutic time window and risk of brain hemorrhage. Different to thrombolytic agents, neuroprotectants reduce neurological injuries by blocking ischemic cascade events such as excitotoxicity and oxidative stress. Nano-neuroprotectants demonstrate higher therapeutic effect than small molecular analogues due to their prolonged circulation lifetime and disrupted blood-brain barrier (BBB) in ischemic region. Even enhanced BBB permeability in ischemic territories is verified, the pore size of ischemic vasculatures determining how large and how efficient the therapeutics can pass is barely studied. In this work, nanoprobes (NPs) with different diameters are developed. In vivo multimodal imaging indicates that NP uptakes in ischemic region depended on their diameters and the pore size upper limit of ischemic vasculatures is determined as 10-11 nm. Additionally, penumbra defined as salvageable ischemic tissues performed a higher BBB permeability than infarct core. This work provides a guideline for developing nano-neuroprotectants by taking advantage of the locally enhanced BBB permeability in ischemic brain tissues.
authors.affiliation: Key Laboratory of Smart Drug Delivery Ministry of Education, School of Pharmacy Fudan University, Shanghai, 201203, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Zheng
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Bai
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Changyi
authors.forename: Xihui
authors.initials: X
authors.lastname: Gao
authors.forename: Wenqing
authors.initials: W
authors.lastname: Zhang
authors.forename: Yuancheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.forename: Shenghong
authors.initials: S
authors.lastname: Ju
authors.forename: Cong
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D064847:Multimodal Imaging; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D010539:Permeability; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: blood-brain barrier; ischemic stroke; multimodal imaging; nanoprobes; vascular pore size