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Biomimetic Dendrimer–Peptide Conjugates for Early Multi‐Target Therapy of Alzheimer's Disease by Inflammatory Microenvironment Modulation
Author(s) -
Liu Peixin,
Zhang Tongyu,
Chen Qinjun,
Li Chao,
Chu Yongchao,
Guo Qin,
Zhang Yiwen,
Zhou Wenxi,
Chen Hongyi,
Zhou Zheng,
Wang Yu,
Zhao Zhenhao,
Luo Yifan,
Li Xuwen,
Song Haolin,
Su Boyu,
Li Chufeng,
Sun Tao,
Jiang Chen
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202100746
Subject(s) - reactive oxygen species , crosstalk , oxidative stress , inflammation , microbiology and biotechnology , peptide , alzheimer's disease , neuroscience , cancer research , immunology , chemistry , biology , disease , medicine , biochemistry , optics , physics
Current therapeutic strategies for Alzheimer's disease (AD) treatments mainly focus on β‐amyloid (Aβ) targeting. However, such therapeutic strategies have limited clinical outcomes due to the chronic and irreversible impairment of the nervous system in the late stage of AD. Recently, inflammatory responses, manifested in oxidative stress and glial cell activation, have been reported as hallmarks in the early stages of AD. Based on the crosstalk between inflammatory response and brain cells, a reactive oxygen species (ROS)‐responsive dendrimer–peptide conjugate (APBP) is devised to target the AD microenvironment and inhibit inflammatory responses at an early stage. With the modification of the targeting peptide, this nanoconjugate can efficiently deliver peptides to the infected regions and restore the antioxidant ability of neurons by activating the nuclear factor (erythroid‐derived 2)‐like 2 signaling pathway. Moreover, this multi‐target strategy exhibits a synergistic function of ROS scavenging, promoting Aβ phagocytosis, and normalizing the glial cell phenotype. As a result, the nanoconjugate can reduce ROS level, decrease Aβ burden, alleviate glial cell activation, and eventually enhance cognitive functions in APPswe/PSEN1dE9 model mice. These results indicate that APBP can be a promising candidate for the multi‐target treatment of AD.