title: Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer's disease mice using magnetic resonance imaging (MRI).
abstract: Diagnosis of Alzheimer's disease (AD) can be performed with the assistance of amyloid imaging. The current method relies on positron emission tomography (PET), which is expensive and exposes people to radiation, undesirable features for a population screening method. Magnetic resonance imaging (MRI) is cheaper and is not radioactive. Our approach uses magnetic nanoparticles (MNPs) made of superparamagnetic iron oxide (SPIO) conjugated with curcumin, a natural compound that specifically binds to amyloid plaques. Coating of curcumin-conjugated MNPs with polyethylene glycol-polylactic acid block copolymer and polyvinylpyrrolidone by antisolvent precipitation in a multi-inlet vortex mixer produces stable and biocompatible curcumin magnetic nanoparticles (Cur-MNPs) with mean diameter <100 nm. These nanoparticles were visualized by transmission electron microscopy and atomic force microscopy, and their structure and chemistry were further characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and Fourier transform infrared spectroscopy. Cur-MNPs exhibited no cytotoxicity in either Madin-Darby canine kidney (MDCK) or differentiated human neuroblastoma cells (SH-SY5Y). The Papp of Cur-MNPs was 1.03 × 10(-6) cm/s in an in vitro blood-brain barrier (BBB) model. Amyloid plaques could be visualized in ex vivo T2*-weighted magnetic resonance imaging (MRI) of Tg2576 mouse brains after injection of Cur-MNPs, and no plaques could be found in non-transgenic mice. Immunohistochemical examination of the mouse brains revealed that Cur-MNPs were co-localized with amyloid plaques. Thus, Cur-MNPs have the potential for non-invasive diagnosis of AD using MRI.
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong Special Administrative Region.
authors.forename: Kwok Kin
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong Special Administrative Region.
authors.forename: Pui Shan
authors.initials: PS
authors.lastname: Chan
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, Departments of Electrical and Electronic Engineering, Medicine and Anatomy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, N.T., Hong Kong Special Administrative Region.
authors.forename: Siu Ming
authors.initials: SM
authors.lastname: Kwan
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, N.T., Hong Kong Special Administrative Region.
authors.forename: King Lun
authors.initials: KL
authors.lastname: Yeung
authors.affiliation: Department of Imaging and Interventional Radiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong Special Administrative Region.
authors.forename: Yì-Xiáng J
authors.initials: YX
authors.lastname: Wáng
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong Special Administrative Region. Electronic address: albert-chow@cuhk.edu.hk.
authors.forename: Albert Hee Lum
authors.initials: AH
authors.lastname: Chow
authors.affiliation: Laboratory of Biomedical Imaging and Signal Processing, Departments of Electrical and Electronic Engineering, Medicine and Anatomy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
authors.forename: Ed X
authors.initials: EX
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong Special Administrative Region. Electronic address: lwbaum@cuhk.edu.hk.
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
mesh_terms: D000327:Adsorption; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis*; D000818:Animals; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D007150:Immunohistochemistry; D061985:Madin Darby Canine Kidney Cells; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000648:ultrastructure; D008822:Mice, Transgenic; D010316:Particle Size; D056951:Photoelectron Spectroscopy; D058225:Plaque, Amyloid / Q000150:complications / Q000175:diagnosis*; D011092:Polyethylene Glycols / Q000737:chemistry; D018629:Spectrometry, Mass, Secondary Ion; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D058185:Magnetite Nanoparticles; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Alzheimer's disease; Amyloid plaques; Curcumin; Iron oxide nanoparticles; MRI; Tg2576 mice