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Carrier-Free Trehalose-Based Nanomotors Targeting Macrophages in Inflammatory Plaque for Treatment of Atherosclerosis
ACS Nano. 2022 Feb 24. doi: 10.1021/acsnano.1c08391.
Ziyu Wu 1 2, Min Zhou 2, Xueting Tang 1, Jiaqi Zeng 2, Yazhou Li 2, Yuning Sun 3, Jia Huang 4, Lin Chen 1, Mimi Wan 1, Chun Mao 1
Abstract:
...Herein, a kind of nitric oxide (NO)-driven carrier-free nanomotor based on the reaction between trehalose (Tr, one of the mTOR-independent autophagy inducers), L-arginine (Arg), and phosphatidylserine (PS) is reported. The developed nanomotors use NO as the driving force, which is generated from the reaction between Arg and excessive reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) specifically presenting in the AS microenvironment. The high expression of ROS and iNOS in the AS site can be used as chemoattractants to induce chemotaxis behavior of the nanomotors to achieve the first-step targeting an AS plaque. Subsequently, the "eat me" signal sent by PS is exploited to precisely target to the macrophages in the AS plaque, realizing the plaque-macrophage-targeted effect by this step-by-step strategy. In vitro and in vivo results confirm that the introduction of the concept of carrier-free nanomotors has greatly improved the biological availability of trehalose (the dose can be reduced from 2.5 g kg-1 in previous reports to 0.01 g kg-1 in this work). Particularly, consumed ROS and the production of NO during the targeting process also play positive roles, in which the former regulates the M2 polarization of macrophages and the latter promotes the reconstruction of an endothelial barrier, which contributes to the multilink treatment of AS.
PMID: 35199998
Tags: atherosclerosis, autophagy, trehalose