Multifunctional peptide-assembled micelles for simultaneously reducing amyloid-β and reactive oxygen species |
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| Authors: | Li Lei Zhifeng Zou Jin Liu Zhiai Xu Ying Fu Yang Tian Wen Zhang |
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| Institution: | School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241 China.; Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062 China.; Department of Chemistry, School of Basic Medical Science, Guizhou Medical University, Guiyang 550025 China ; Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge CB3 0AS UK |
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| Abstract: | The excessive production and deposition of amyloid-β (Aβ) is one of the most important etiologies of Alzheimer''s disease (AD). The interaction between Aβ and metal ions produces aberrant reactive oxygen species (ROS), which induce oxidative stress and accelerate the progression of AD. To reduce Aβ plaques and ROS to maintain their homeostasis is an emerging and ingenious strategy for effective treatment of AD. Herein, we report the rational design of multifunctional micelles (MPGLT) based on a polymer-grafted peptide to simultaneously clear Aβ and ROS for AD therapy. The MPGLT integrating three functional peptides as a ROS scavenger (tk-GSH), β-sheet breaker (LP) and an autophagy activator (TK) respectively, could capture and degrade Aβ. Meanwhile, the tk-GSH on the surface of MPGLT effectively scavenges the intracellular ROS. Consequently, MPGLT reduced the cytotoxicity of Aβ and ROS. In vivo animal studies using an AD mouse model further showed that MPGLT could transport across the blood–brain barrier for decreasing the Aβ plaque and eliminating ROS in vivo. This peptide micelle-based synergistic strategy may provide novel insight for AD therapy.Multifunctional micelles based on a peptide–polymer for simultaneously targeting Aβ degradation and ROS scavenging for AD therapy. |
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