PMID- 37713364
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231025
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Linking)
VI  - 17
IP  - 18
DP  - 2023 Sep 26
TI  - Enhanced Biohomogeneous Composite Membrane-Encapsulated Nanoplatform with 
      Podocyte Targeting for Precise and Safe Treatment of Diabetic Nephropathy.
PG  - 18037-18054
LID - 10.1021/acsnano.3c04671 [doi]
AB  - Diabetic nephropathy (DN), associated with high mobility and disability, is the 
      leading cause of end-stage kidney disease worldwide. Dysfunction of the mammalian 
      target of the rapamycin (mTOR) pathway and reactive oxygen species (ROS) 
      activation in the glomeruli is the main hypnosis for DN progression. However, the 
      use of mTOR inhibitors for DN treatment remains controversial. In this study, we 
      built a multifunctional selective mechanistic target of rapamycin complex 1 
      (mTORC1) inhibiting nanoplatform (naming as ESC-HCM-B) that targets the release 
      of mTOR and ROS inhibitors near podocytes, aiming to confirm whether combination 
      therapy is an alternative method for DN treatment. The results showed that 
      ESC-HCM-B achieved high drug loading because of the core mesoporous silica 
      nanoparticles (MSNPs), and the enhanced biohomogeneous composite membrane endowed 
      ESC-HCM-B with the characteristics of avoiding immune phagocytosis, automatic 
      valve-type slow-release drug, and high stability. In vitro, the nanoplatform 
      showed high efficiency in podocyte targeting but no significant cytotoxicity or 
      apoptotic promotion. In particular, the quantum dots carried by ESC-HCM-B further 
      amplified the effect of "nanoenzyme"; this mechanism reduced the ROS level in 
      podocytes induced by high glucose, protected mitochondrial damage, and restored 
      mitochondrial energy metabolism. In vivo, the nanoplatform specifically targeted 
      the glomerular and podocyte regions of the kidney. After treatment, the 
      nanoplatform significantly reduced urinary protein levels and delayed 
      glomerulosclerosis in DN rats. This nanoplatform provides a safe and effective 
      strategy for DN treatment.
FAU - Fan, Kui
AU  - Fan K
AD  - Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400010, China.
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing, 400010, China.
FAU - Yuan, Shiyi
AU  - Yuan S
AD  - Department of Hematology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400010, China.
AD  - Department of Nephrology, Chongqing Yongchuan District People's Hospital, 
      Chongqing, 402160, China.
FAU - Zhou, Mi
AU  - Zhou M
AD  - Department of Biochemistry and Molecular Biology, Army Medical University, 
      Chongqing, 400038, China.
FAU - Yu, Yuan
AU  - Yu Y
AD  - Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400010, China.
FAU - Guo, Jing
AU  - Guo J
AD  - Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing 
      University, Chongqing, 400030, China.
FAU - Fang, Liang
AU  - Fang L
AD  - Department of Nephrology, Yongchuan Hospital of Chongqing Medical University, 
      Chongqing, 402160, China.
FAU - Zhou, Chanjuan
AU  - Zhou C
AD  - Department of Nephrology, Yongchuan Hospital of Chongqing Medical University, 
      Chongqing, 402160, China.
FAU - Cui, Peijin
AU  - Cui P
AD  - Chongqing Key Laboratory of Cerebral Vascular Disease Research, Yongchuan 
      Hospital of Chongqing Medical University, Chongqing, 402160, China.
FAU - Zhang, Siliang
AU  - Zhang S
AD  - Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400010, China.
FAU - Li, Rong
AU  - Li R
AD  - Department of Nephrology, Guangyuan Central Hospital, Guanyuan, 628000, China.
FAU - Wang, Zhigang
AU  - Wang Z
AD  - Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing 
      Medical University, Chongqing, 400010, China.
FAU - Zhong, Ling
AU  - Zhong L
AUID- ORCID: 0000-0002-4206-514X
AD  - Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400010, China.
FAU - Zeng, Li
AU  - Zeng L
AUID- ORCID: 0000-0002-5016-6557
AD  - Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing, 400010, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230915
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Podocytes/metabolism
MH  - *Diabetic Nephropathies/drug therapy/etiology/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Apoptosis
MH  - TOR Serine-Threonine Kinases/metabolism/pharmacology/therapeutic use
MH  - Mammals/metabolism
MH  - *Diabetes Mellitus/metabolism
OTO - NOTNLM
OT  - diabetic nephropathy
OT  - glomerulosclerosis
OT  - mammalian target of rapamycin (mTOR)
OT  - nano enzyme
OT  - podocyte targeting
OT  - reactive oxygen species (ROS)
EDAT- 2023/09/15 18:42
MHDA- 2023/10/23 01:18
CRDT- 2023/09/15 13:23
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/09/15 18:42 [pubmed]
PHST- 2023/09/15 13:23 [entrez]
AID - 10.1021/acsnano.3c04671 [doi]
PST - ppublish
SO  - ACS Nano. 2023 Sep 26;17(18):18037-18054. doi: 10.1021/acsnano.3c04671. Epub 2023 
      Sep 15.