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Metal–Organic Frameworks Harness Cu Chelating and Photooxidation Against Amyloid β Aggregation in Vivo
Author(s) -
Yu Dongqin,
Guan Yijia,
Bai Fuquan,
Du Zhi,
Gao Nan,
Ren Jinsong,
Qu Xiaogang
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201805835
Subject(s) - chelation , in vivo , biocompatibility , chemistry , metal organic framework , cytotoxicity , amyloid (mycology) , combinatorial chemistry , neurotoxicity , biophysics , metal , nanotechnology , materials science , in vitro , adsorption , organic chemistry , biochemistry , toxicity , inorganic chemistry , biology , microbiology and biotechnology
Recently, photooxygenation of amyloid β (Aβ) has emerged as an effective way to inhibit Aβ aggregation in Alzheimer's disease (AD) treatment. However, their further application has been highly obstructed by self‐aggregation, no metal chelating ability, and poor protein‐enrichment capacity. Herein, porphyrinic metal–organic frameworks (PMOFs) are utilized as a superior Cu II chelating and photooxidation agent for inhibiting Aβ aggregation. We selected only four classical kinds of POMFs (Zr–MOF, Al–MOF, Ni–MOF, Hf–MOF) for further investigation in our study, which are stable in physiological conditions and exhibit excellent biocompatibility. Among them, Hf–MOF was the most efficient Aβ photooxidant. A possible explanation about the difference in capacity of 1 O 2 generation of these four PMOFs has been provided according to the experimental results and DFT calculations. Furthermore, Hf–MOFs are modified with Aβ‐targeting peptide, LPFFD. This can not only enhance Hf–MOFs targeting cellular Aβ to decrease Aβ‐induced cytotoxicity, but also improve Aβ photooxidation in the complicated living environment. More intriguingly, in vivo studies indicate that the well‐designed LPFFD modified Hf–MOFs can decrease Aβ‐induced neurotoxicity and extend the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Our work may open a new avenue for using MOFs as neurotoxic‐metal‐chelating and photo‐therapeutic agents for AD treatment.