PMID- 38095305
OWN - NLM
STAT- MEDLINE
DCOM- 20240118
LR  - 20240118
IS  - 1530-6992 (Electronic)
IS  - 1530-6984 (Linking)
VI  - 24
IP  - 2
DP  - 2024 Jan 17
TI  - Reducing Cholesterol Level in Live Macrophages Improves Delivery Performance by 
      Enhancing Blood Shear Stress Adaptation.
PG  - 607-616
LID - 10.1021/acs.nanolett.3c03569 [doi]
AB  - In recent years, live-cell-based drug delivery systems have gained considerable 
      attention. However, shear stress, which accompanies blood flow, may cause cell 
      death and weaken the delivery performance. In this study, we found that reducing 
      cholesterol in macrophage plasma membranes enhanced their tumor targeting ability 
      by more than 2-fold. Our study demonstrates that the reduced cholesterol level 
      deactivated the mammalian target of rapamycin (mTOR) and consequently promoted 
      the nuclear translocation of transcription factor EB (TFEB), which in turn 
      enhanced the expression of superoxide dismutase (SOD) to reduce reactive oxygen 
      species (ROS) induced by shear stress. A proof-of-concept system using low 
      cholesterol macrophages attached to MXene (e.g., l-RX) was fabricated. In a 
      melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors 
      with no recurrences observed in mice. Therefore, cholesterol reduction is a 
      simple and effective way to enhance the targeting performance of macrophage-based 
      drug delivery systems.
FAU - Zhang, Mengxing
AU  - Zhang M
AD  - Med-X center for Materials, College of Polymer Science and Engineering, Sichuan 
      University, Chengdu 610065, China.
FAU - Li, Jing
AU  - Li J
AD  - Institute of Systems Epidemiology, West China School of Public Health and West 
      China Fourth Hospital, Sichuan University, Chengdu 610041, China.
FAU - Ji, Na
AU  - Ji N
AD  - Institute of Systems Epidemiology, West China School of Public Health and West 
      China Fourth Hospital, Sichuan University, Chengdu 610041, China.
FAU - Bao, Qixue
AU  - Bao Q
AD  - Institute of Systems Epidemiology, West China School of Public Health and West 
      China Fourth Hospital, Sichuan University, Chengdu 610041, China.
FAU - Sun, Ningyun
AU  - Sun N
AD  - Institute of Systems Epidemiology, West China School of Public Health and West 
      China Fourth Hospital, Sichuan University, Chengdu 610041, China.
FAU - Rong, Hongding
AU  - Rong H
AD  - Institute of Systems Epidemiology, West China School of Public Health and West 
      China Fourth Hospital, Sichuan University, Chengdu 610041, China.
FAU - Peng, Xu
AU  - Peng X
AD  - Institute of Systems Epidemiology, West China School of Public Health and West 
      China Fourth Hospital, Sichuan University, Chengdu 610041, China.
FAU - Yang, Lan
AU  - Yang L
AD  - Med-X center for Materials, College of Polymer Science and Engineering, Sichuan 
      University, Chengdu 610065, China.
FAU - Xie, Mingxin
AU  - Xie M
AD  - Institute of Systems Epidemiology, West China School of Public Health and West 
      China Fourth Hospital, Sichuan University, Chengdu 610041, China.
FAU - He, Shanshan
AU  - He S
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, Sichuan University, Chengdu 610065, 
      China.
FAU - Lin, Qing
AU  - Lin Q
AUID- ORCID: 0000-0001-9598-9111
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, Sichuan University, Chengdu 610065, 
      China.
FAU - Zhang, Zhirong
AU  - Zhang Z
AUID- ORCID: 0000-0001-9118-5394
AD  - Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of 
      Education, West China School of Pharmacy, Sichuan University, Chengdu 610065, 
      China.
FAU - Li, Lin
AU  - Li L
AD  - Institute of Systems Epidemiology, West China School of Public Health and West 
      China Fourth Hospital, Sichuan University, Chengdu 610041, China.
FAU - Zhang, Ling
AU  - Zhang L
AUID- ORCID: 0000-0003-3237-4544
AD  - Med-X center for Materials, College of Polymer Science and Engineering, Sichuan 
      University, Chengdu 610065, China.
LA  - eng
PT  - Journal Article
DEP - 20231214
PL  - United States
TA  - Nano Lett
JT  - Nano letters
JID - 101088070
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Reactive Oxygen Species/metabolism
MH  - *Macrophages/metabolism
MH  - *Superoxide Dismutase
MH  - Drug Delivery Systems
MH  - Cholesterol/metabolism
MH  - Mammals/metabolism
OTO - NOTNLM
OT  - cholesterol
OT  - live cell delivery system
OT  - mTORC1
OT  - reactive oxygen species
OT  - shear stress
EDAT- 2023/12/14 12:42
MHDA- 2024/01/18 06:42
CRDT- 2023/12/14 07:53
PHST- 2024/01/18 06:42 [medline]
PHST- 2023/12/14 12:42 [pubmed]
PHST- 2023/12/14 07:53 [entrez]
AID - 10.1021/acs.nanolett.3c03569 [doi]
PST - ppublish
SO  - Nano Lett. 2024 Jan 17;24(2):607-616. doi: 10.1021/acs.nanolett.3c03569. Epub 
      2023 Dec 14.