정희정 (University of Illinois at Urbana-Champaign) | 한빛사논문 > 한빛사

한빛사논문

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University of Illinois at Urbana-Champaign

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Nano Lett., Nov 22 2023, | https://doi.org/10.1021/acs.nanolett.3c03222 Intracerebral Nanoparticle Transport Facilitated by Alzheimer Pathology and Age

Gregory C Tracy ¹, Kai-Yu Huang ², Yu-Tong Hong ², Shengzhe Ding ², Hayden A Noblet ^1,3, Ki H Lim ¹, Eung Chang Kim ¹, Hee Jung Chung ^1,4,5,3, Hyunjoon Kong ^2,4,5,3,6

¹Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

²Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

³Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

⁴Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

⁵Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

⁶KU-KIST Graduate School of Converging Science and Technology, Korea University, Seongbuk-gu, Seoul 02841, South Korea.

G.C.T., K.-Y.H., and Y.-T.H. contributed equally.

Corresponding Authors: Hee Jung Chung, Hyunjoon Kong

Abstract

Nanoparticles have emerged as potential transporters of drugs targeting Alzheimer's disease (AD), but their design should consider the blood-brain barrier (BBB) integrity and neuroinflammation of the AD brain. This study presents that aging is a significant factor for the brain localization and retention of nanoparticles, which we engineered to bind with reactive astrocytes and activated microglia. We assembled 200 nm-diameter particles using a block copolymer of poly(lactic-co-glycolic acid) (PLGA) and CD44-binding hyaluronic acid (HA). The resulting PLGA-b-HA nanoparticles displayed increased binding to CD44-expressing reactive astrocytes and activated microglia. Upon intravascular injection, nanoparticles were localized to the hippocampi of both APP/PS1 AD model mice and their control littermates at 13-16 months of age due to enhanced transvascular transport through the leaky BBB. No particles were found in the hippocampi of young adult mice. These findings demonstrate the brain localization of nanoparticles due to aging-induced BBB breakdown regardless of AD pathology.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-23)
연구진국외 연구진
분야 바이오·의료융합 > 바이오소재

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