김도경 (경희대학교 의과대학)

한빛사논문

조회554

경희대학교 의과대학

CV File 38 kb

Bioact. Mater., Available online 9 January 2023 | https://doi.org/10.1016/j.bioactmat.2023.01.006 Potential Alzheimer's disease therapeutic nano-platform: Discovery of amyloid-beta plaque disaggregating agent and brain-targeted delivery system using porous silicon nanoparticles

Jaehoon Kim^a,1, Hyeji Um^a,1, Na Hee Kim^a, Dokyoung Kim^a,b,c,d,e,f

^aDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
^bMedical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Kyung Hee University, Seoul, 02447, Republic of Korea
^cDepartment of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea
^dCenter for Converging Humanities, Kyung Hee University, Seoul, 02447, Republic of Korea
^eKHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, 02447, Republic of Korea
^fUC San Diego Materials Research Science and Engineering Center, 9500 Gilman Drive La Jolla, CA, 92093, USA

¹These authors contributed equally.
Corresponding author: Dokyoung Kim

Abstract

There has been a lot of basic and clinical research on Alzheimer's disease (AD) over the last 100 years, but its mechanisms and treatments have not been fully clarified. Despite some controversies, the amyloid-beta hypothesis is one of the most widely accepted causes of AD. In this study, we disclose a new amyloid-beta plaque disaggregating agent and an AD brain-targeted delivery system using porous silicon nanoparticles (pSiNPs) as a therapeutic nano-platform to overcome AD. We hypothesized that the negatively charged sulfonic acid functional group could disaggregate plaques and construct a chemical library. As a result of the in vitro assay of amyloid plaques and library screening, we confirmed that 6-amino-2-naphthalenesulfonic acid (ANA) showed the highest efficacy for plaque disaggregation as a hit compound. To confirm the targeted delivery of ANA to the AD brain, a nano-platform was created using porous silicon nanoparticles (pSiNPs) with ANA loaded into the pore of pSiNPs and biotin-polyethylene glycol (PEG) surface functionalization. The resulting nano-formulation, named Biotin-CaCl2-ANA-pSiNPs (BCAP), delivered a large amount of ANA to the AD brain and ameliorated memory impairment of the AD mouse model through the disaggregation of amyloid plaques in the brain. This study presents a new bioactive small molecule for amyloid plaque disaggregation and its promising therapeutic nano-platform for AD brain-targeted delivery.

논문정보

형식Research article
게재일2023년 01월 (BRIC 등록일 2023-01-12)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

댓글 작성 로그인

CV 열람하기

연락처 보기