PMID- 35199998
OWN - NLM
STAT- MEDLINE
DCOM- 20220418
LR  - 20220418
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Linking)
VI  - 16
IP  - 3
DP  - 2022 Mar 22
TI  - Carrier-Free Trehalose-Based Nanomotors Targeting Macrophages in Inflammatory 
      Plaque for Treatment of Atherosclerosis.
PG  - 3808-3820
LID - 10.1021/acsnano.1c08391 [doi]
AB  - Inducing autophagy of macrophages to improve abnormal lipid metabolism is an 
      important way to treat atherosclerosis (AS). Yet, the current application of the 
      mammalian target of rapamycin (mTOR)-dependent autophagy inducers is limited by 
      the side effects and lack of targeting and low biological availability. 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.
FAU - Wu, Ziyu
AU  - Wu Z
AD  - National and Local Joint Engineering Research Center of Biomedical Functional 
      Materials, School of Chemistry and Materials Science, Nanjing Normal University, 
      Nanjing 210023, China.
AD  - Department of Vascular Surgery, Affiliated Drum Tower Hospital, Medical School of 
      Nanjing University, Nanjing 210008, China.
FAU - Zhou, Min
AU  - Zhou M
AD  - Department of Vascular Surgery, Affiliated Drum Tower Hospital, Medical School of 
      Nanjing University, Nanjing 210008, China.
FAU - Tang, Xueting
AU  - Tang X
AD  - National and Local Joint Engineering Research Center of Biomedical Functional 
      Materials, School of Chemistry and Materials Science, Nanjing Normal University, 
      Nanjing 210023, China.
FAU - Zeng, Jiaqi
AU  - Zeng J
AD  - Department of Vascular Surgery, Affiliated Drum Tower Hospital, Medical School of 
      Nanjing University, Nanjing 210008, China.
FAU - Li, Yazhou
AU  - Li Y
AD  - Department of Vascular Surgery, Affiliated Drum Tower Hospital, Medical School of 
      Nanjing University, Nanjing 210008, China.
FAU - Sun, Yuning
AU  - Sun Y
AD  - Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for 
      Pediatric Research, Shanghai Jiao Tong University, School of Medicine, Shanghai 
      200092, China.
FAU - Huang, Jia
AU  - Huang J
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai 
      Institute of Cardiovascular Diseases, Shanghai 200032, China.
FAU - Chen, Lin
AU  - Chen L
AD  - National and Local Joint Engineering Research Center of Biomedical Functional 
      Materials, School of Chemistry and Materials Science, Nanjing Normal University, 
      Nanjing 210023, China.
FAU - Wan, Mimi
AU  - Wan M
AUID- ORCID: 0000-0002-8686-7961
AD  - National and Local Joint Engineering Research Center of Biomedical Functional 
      Materials, School of Chemistry and Materials Science, Nanjing Normal University, 
      Nanjing 210023, China.
FAU - Mao, Chun
AU  - Mao C
AUID- ORCID: 0000-0003-4085-3414
AD  - National and Local Joint Engineering Research Center of Biomedical Functional 
      Materials, School of Chemistry and Materials Science, Nanjing Normal University, 
      Nanjing 210023, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220224
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (Reactive Oxygen Species)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 94ZLA3W45F (Arginine)
RN  - B8WCK70T7I (Trehalose)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Arginine/pharmacology
MH  - *Atherosclerosis/drug therapy/metabolism
MH  - Autophagy
MH  - Humans
MH  - Macrophages/metabolism
MH  - Nitric Oxide/pharmacology
MH  - *Plaque, Atherosclerotic
MH  - Reactive Oxygen Species/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism/pharmacology
MH  - Trehalose/pharmacology
OTO - NOTNLM
OT  - atherosclerosis
OT  - autophagy
OT  - carrier-free
OT  - macrophage
OT  - nanomotor
OT  - trehalose
EDAT- 2022/02/25 06:00
MHDA- 2022/04/19 06:00
CRDT- 2022/02/24 12:18
PHST- 2022/02/25 06:00 [pubmed]
PHST- 2022/04/19 06:00 [medline]
PHST- 2022/02/24 12:18 [entrez]
AID - 10.1021/acsnano.1c08391 [doi]
PST - ppublish
SO  - ACS Nano. 2022 Mar 22;16(3):3808-3820. doi: 10.1021/acsnano.1c08391. Epub 2022 
      Feb 24.