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한국과학기술연구원 (KIST)

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Adv. Funct. Mater., First published: 17 February 2020 | https://doi.org/10.1002/adfm.201910475 Silica Nanodepletors: Targeting and Clearing Alzheimer's β‐Amyloid Plaques

Huijin Jung^a,b, You Jung Chung^c, Rosemarie Wilton^d, Chang Heon Lee^c, Byung Il Lee^c, Jinyeong Lim^e, Hyojin Lee^f, Jong-Ho Choi^b, Hyuno Kang^g, Byeongdu Lee^h, Elena A. Rozhkova^i,* Chan Beum Park^c,* and Joonseok Lee^a,*

^aMolecular Recognition Research Center, Korea Institute of Science and Technology (KIST), Department of HY-KIST Bio-convergence, Hanyang University, Seoul 02792, Republic of Korea
^bDepartment of Chemistry, Korea University, Seoul 02841, Republic of Korea
^cDepartment of Materials Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
^dBiosciences, Argonne National Laboratory, Argonne, IL 60439, USA
^eGwangju Center, Korea Basic Science Institute (KBSI), Gwangju 61186, Republic of Korea
^fCenter for Biomaterials, Biomedical Research Institute, KIST, Seoul 02792, Republic of Korea
^gDivision of Analytical Science, Korea Basic Science Institute (KBSI), Daejeon 34133, Republic of Korea
^hX-ray Science Division, Argonne National Laboratory, Argonne, IL 60439, USA
ⁱCenter for Nanoscale Materials, Argonne National Laboratory, Argonne, IL 60439, USA

H.J., Y.J.C., R.W., and C.H.L. contributed equally to this work.

^*To whom correspondence should be addressed.

Abstract

Abnormal accumulation of β‐amyloid (Aβ) peptide aggregates in the brain is a major hallmark of Alzheimer's disease (AD). Aβ aggregates interfere with neuronal communications, ultimately causing neuronal damage and brain atrophy. Much effort has been made to develop AD treatments that suppress Aβ aggregate formation, thereby attenuating Aβ‐induced neurotoxicity. Here, the design of Aβ nanodepletors consisting of ultralarge mesoporous silica nanostructures and anti‐Aβ single‐chain variable fragments, with the goal of targeting and eliminating aggregative Aβ monomers, is reported. The Aβ nanodepletors impart a notable decline in Aβ aggregate formation, resulting in significant mitigation of Aβ‐induced neurotoxicity in vitro. Furthermore, stereotaxic injections of Aβ nanodepletors into the brain of an AD mouse model system successfully suppress Aβ plaque formation in vivo up to ≈30%, suggesting that Aβ nanodepletors can serve as a promising antiamylodoisis material.

Keywords : β‐amyloid peptides, Alzheimer's disease, nanodepletors, scFvm, silica nanostructures

논문정보

형식Research article
게재일2020년 02월 (BRIC 등록일 2020-03-12)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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