Blood-brain barrier-penetrating nanotheranostics for acute and chronic neurodegenerative diseases and the like
AssigneeThe Governing Council of the University of Toronto
InventorsXiaoyu Wu, Chunsheng He, Azhar Abbasi, Taksim Ahmed, Jeffrey Henderson, Ping Cai
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Abstract
Brain-targeted (BT) and ROS-activable nanoconstructs (NC) comprising a metal oxide nanoparticle embedded in a matrix of lipid and a brain targeted polymer (BTP)/platform configured to facilitate blood brain barrier (BBB) penetration and accumulation in a disease area of the central nervous system (CNS), as well as compositions having the BT and ROS-activable NC and methods of using the BT and ROS-activable NC to treat and diagnose a CNS disease or condition.
Claims23
A theranostic nanoparticle for detecting a central nervous system (CNS) disease area behind the blood-brain barrier (BBB) and reducing reactive oxygen species (ROS) and oxidative stress in the CNS disease area, the theranostic nanoparticle comprising a metal oxide nanoparticle wherein the metal oxide acts both as (i) a contrast agent that reacts with hydrogen peroxide to produce paramagnetic ions that improve magnetic resonance imagining contrast and (ii) a therapeutic agent that reduces ROS and oxidative stress in the CNS disease area, the metal oxide nanoparticle being embedded in a matrix of lipids and a brain targeted polymer (BTP) that facilitates crossing the BBB and binds to the paramagnetic ions, and a functional moiety conjugated onto the BTP that binds to and/or complexes to a biomarker of the CNS disease thereby facilitating BBB penetration and accumulation of the theranostic nanoparticle in the disease area of the CNS,
- wherein the theranostic nanoparticle has a negative surface charge.
A method of preparing theranostic nanoparticles for detecting a central nervous system (CNS) disease area behind the blood-brain barrier (BBB) and reducing ROS and oxidative stress in the CNS disease area, the method comprising of steps of (a) coating metal oxide nanoparticles with a lipid or a polymer to obtain hydrophobic or hydrophilic nanoparticle surface, the metal oxide being reactive with hydrogen peroxide to produce paramagnetic ions that improve magnetic resonance imaging contrast;
- (b) mixing the coated metal oxide nanoparticles and a brain targeted polymer in a lipid matrix to form an emulsion, wherein the brain targeted polymer binds to the paramagnetic ions, and (c) ultrasonicating or high pressure homogenizing the emulsion to form the theranostic nanoparticles having a negative surface charge.
Dependencies are inferred from the claim text.