PMID- 36627264
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230330
IS  - 1613-6829 (Electronic)
IS  - 1613-6810 (Linking)
VI  - 19
IP  - 10
DP  - 2023 Mar
TI  - Clustered Cobalt Nanodots Initiate Ferroptosis by Upregulating Heme Oxygenase 1 
      for Radiotherapy Sensitization.
PG  - e2206415
LID - 10.1002/smll.202206415 [doi]
AB  - High cobalt (Co) levels in tumors are associated with good clinical prognosis. An 
      anticancer regimen that increases intratumoral Co through targeted nanomaterial 
      delivery is proposed in this study. Bovine serum albumin and cobalt dichloride 
      are applied to prepare cobaltous oxide nanodots using a facile biomineralization 
      strategy. After iRGD peptide conjugation, the nanodots are loaded into dendritic 
      mesoporous silica nanoparticles, generating a biocompatible product iCoDMSN. This 
      nanocomposite accumulates in tumors after intravenous injection by deep tissue 
      penetration and can be used for photoacoustic imaging. Proteomics research and 
      molecular biology experiments reveal that iCoDMSN is a potent ferroptosis inducer 
      in cancer cells. Mechanistically, iCoDMSNs upregulate heme oxygenase 1 (HMOX1), 
      which increases transferrin receptors and reduces solute carrier family 40 member 
      1 (SLC40A1), resulting in Fe(2+) accumulation and ferroptosis initiation. 
      Furthermore, upregulated nuclear factor erythroid 2-related factor 2 (NRF2), 
      arising from the reduction in Kelch-like ECH-associated protein 1 (KEAP1) 
      expression, is responsible for HMOX1 enhancement after iCoDMSN treatment. Owing 
      to intensified ferroptosis, iCoDMSN acts as an efficient radiotherapy enhancer to 
      eliminate cancer cells in vitro and in vivo. This study demonstrates a versatile 
      Co-based nanomaterial that primes ferroptosis by expanding the labile iron pool 
      in cancer cells, providing a promising tumor radiotherapy sensitizer.
CI  - (c) 2023 Wiley-VCH GmbH.
FAU - Zhao, Jianqi
AU  - Zhao J
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Chen, Yin
AU  - Chen Y
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Xiong, Tainong
AU  - Xiong T
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Han, Songling
AU  - Han S
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Li, Chenwenya
AU  - Li C
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - He, Yingjuan
AU  - He Y
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - He, Yongwu
AU  - He Y
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Zhao, Gaomei
AU  - Zhao G
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Wang, Tao
AU  - Wang T
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Wang, Liting
AU  - Wang L
AD  - Biomedical Analysis Center, Third Military Medical University, Chongqing, 400038, 
      P. R. China.
FAU - Cheng, Tianmin
AU  - Cheng T
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Wang, Cheng
AU  - Wang C
AUID- ORCID: 0000-0002-6690-6433
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
FAU - Wang, Junping
AU  - Wang J
AD  - State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined 
      Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of 
      Preventive Medicine, Third Military Medical University, Chongqing, 400038, P. R. 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230110
PL  - Germany
TA  - Small
JT  - Small (Weinheim an der Bergstrasse, Germany)
JID - 101235338
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - 3G0H8C9362 (Cobalt)
SB  - IM
MH  - Humans
MH  - *Ferroptosis
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Heme Oxygenase-1/metabolism
MH  - *Neoplasms
MH  - Cobalt
OTO - NOTNLM
OT  - cobaltous oxide
OT  - dendritic mesoporous silica
OT  - ferroptosis
OT  - heme oxygenase 1
OT  - radiotherapy sensitizers
EDAT- 2023/01/11 06:00
MHDA- 2023/03/15 06:00
CRDT- 2023/01/10 23:02
PHST- 2022/12/18 00:00 [revised]
PHST- 2022/10/19 00:00 [received]
PHST- 2023/01/11 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/01/10 23:02 [entrez]
AID - 10.1002/smll.202206415 [doi]
PST - ppublish
SO  - Small. 2023 Mar;19(10):e2206415. doi: 10.1002/smll.202206415. Epub 2023 Jan 10.