PMID- 38157218
OWN - NLM
STAT- MEDLINE
DCOM- 20240117
LR  - 20240117
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Linking)
VI  - 18
IP  - 2
DP  - 2024 Jan 16
TI  - Targeted Degradation of Signal Transduction and Activator of Transcription 3 by 
      Chaperone-Mediated Autophagy Targeting Chimeric Nanoplatform.
PG  - 1599-1610
LID - 10.1021/acsnano.3c09536 [doi]
AB  - Chaperone-mediated autophagy (CMA) is a lysosomal-dependent proteolysis pathway 
      for the degradation of cytosolic proteins. However, exploiting CMA-mediated 
      proteolysis to degrade proteins of interest in cancer therapy has not been widely 
      applied. In this study, we develop a CMA-targeting chimera (CMATAC) to 
      efficiently and specifically degrade signal transduction and activator of 
      transcription 3 (STAT3) in tumor cells. CMATAC consists of STAT3 and heat shock 
      cognate 70 kDa protein (HSC70) targeting peptides connected by a linker. To 
      efficiently deliver CMATACs into tumor cells, lipid nanoparticles (LNPs) are used 
      to encapsulate CMATACs (nCMATACs) and decorated with an insulin-like growth 
      factor 2 receptor (IGF2R) targeting peptide (InCMATACs) to achieve tumor 
      targeting and precise delivery. The CMA pathway is activated in tumor cells by a 
      fasting-mimicking diet (FMD). Furthermore, FMD treatment strongly enhances the 
      cellular uptake and tumor accumulation of InCMATACs by upregulating the IGF2R 
      expression. As a result, InCMATACs efficiently degrade STAT3 protein in both A549 
      and HCC827 tumor cells and inhibit tumor growths in vivo. This study demonstrates 
      that InCMATACs can be used for selective proteolysis in cancer therapy.
FAU - Song, Haohao
AU  - Song H
AD  - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS 
      Center for Excellence in Nanoscience, National Center for Nanoscience and 
      Technology, Beijing 100190, China.
AD  - Henan Institutes of Advanced Technology, Zhengzhou University, Zhengzhou 450052, 
      China.
FAU - Huang, Wenping
AU  - Huang W
AD  - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS 
      Center for Excellence in Nanoscience, National Center for Nanoscience and 
      Technology, Beijing 100190, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Jia, Fuhao
AU  - Jia F
AD  - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS 
      Center for Excellence in Nanoscience, National Center for Nanoscience and 
      Technology, Beijing 100190, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Wang, Zhihang
AU  - Wang Z
AD  - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS 
      Center for Excellence in Nanoscience, National Center for Nanoscience and 
      Technology, Beijing 100190, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Zhang, Jie
AU  - Zhang J
AD  - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS 
      Center for Excellence in Nanoscience, National Center for Nanoscience and 
      Technology, Beijing 100190, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Qian, Ruihao
AU  - Qian R
AD  - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS 
      Center for Excellence in Nanoscience, National Center for Nanoscience and 
      Technology, Beijing 100190, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Nie, Gungjun
AU  - Nie G
AUID- ORCID: 0000-0001-5040-9793
AD  - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS 
      Center for Excellence in Nanoscience, National Center for Nanoscience and 
      Technology, Beijing 100190, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Wang, Hai
AU  - Wang H
AUID- ORCID: 0000-0002-1292-998X
AD  - CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS 
      Center for Excellence in Nanoscience, National Center for Nanoscience and 
      Technology, Beijing 100190, China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
LA  - eng
PT  - Journal Article
DEP - 20231229
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (Peptides)
SB  - IM
MH  - Humans
MH  - *Chaperone-Mediated Autophagy
MH  - Autophagy
MH  - *Neoplasms/metabolism
MH  - Proteolysis
MH  - HSC70 Heat-Shock Proteins/metabolism
MH  - Peptides/metabolism
MH  - Signal Transduction
MH  - Lysosomes/metabolism
OTO - NOTNLM
OT  - STAT3
OT  - chaperone-mediated autophagy
OT  - lipid nanoparticles
OT  - protein degradation
OT  - targeted delivery
EDAT- 2024/01/02 11:42
MHDA- 2024/01/17 06:42
CRDT- 2023/12/29 11:33
PHST- 2024/01/17 06:42 [medline]
PHST- 2024/01/02 11:42 [pubmed]
PHST- 2023/12/29 11:33 [entrez]
AID - 10.1021/acsnano.3c09536 [doi]
PST - ppublish
SO  - ACS Nano. 2024 Jan 16;18(2):1599-1610. doi: 10.1021/acsnano.3c09536. Epub 2023 
      Dec 29.