PMID- 37822991
OWN - NLM
STAT- MEDLINE
DCOM- 20231015
LR  - 20231018
IS  - 1178-2013 (Electronic)
IS  - 1176-9114 (Print)
IS  - 1176-9114 (Linking)
VI  - 18
DP  - 2023
TI  - The Therapeutic Effects of MUC1-C shRNA@Fe(3)O(4) Magnetic Nanoparticles in 
      Alternating Magnetic Fields on Triple-Negative Breast Cancer.
PG  - 5651-5670
LID - 10.2147/IJN.S426849 [doi]
AB  - PURPOSE: Improving the treatment of triple-negative breast cancer (TNBC) is a 
      serious challenge today. The primary objective of this study was to construct 
      MUC1-C shRNA@ Fe(3)O(4) magnetic nanoparticles (MNPs) and investigate their 
      potential therapeutic benefits in alternating magnetic fields (AMF) on TNBC. 
      METHODS: Firstly, we verified the high expression of MUC1 in TNBC and synthesized 
      specific MUC1-C shRNA plasmids (MUC1-C shRNA). Then, we prepared and 
      characterized MUC1-C shRNA@Fe(3)O(4) MNPs and confirmed their MUC1-C gene 
      silencing effect and magneto-thermal conversion ability in AMF. Moreover, the 
      inhibitory effects on TNBC in vitro and in vivo were observed as well as 
      biosafety. Finally, the protein levels of BCL-2-associated X protein (Bax), 
      cleaved-caspase3, glutathione peroxidase inhibitor 4 (GPX4), nuclear factor 
      erythroid 2-related factor 2 (NRF2), and ferritin heavy chain 1 (FTH1) in TNBC 
      cells and tissues were examined, and it was speculated that apoptosis and 
      ferroptosis were involved in the synergistic treatment. RESULTS: MUC1-C shRNA@ 
      Fe(3)O(4) MNPs have a size of ~75 nm, with an encapsulation rate of (29.78+/-0.63) 
      %, showing excellent gene therapy and magnetic hyperthermia functions. Under a 
      constant AMF (3Kw) and a set concentration (200microg mL(-1)), the nanoparticles 
      could be rapidly warmed up within 20 minutes and stabilized at about 43  degrees C. It 
      could be uptaken by TNBC cells through endocytosis and significantly inhibit 
      their proliferation and migration, with a growth inhibition rate of 79.22% for 
      TNBC tumors. After treatment, GPX4, NRF2, and FTH1 expression levels in TNBC 
      cells and tumor tissues were suppressed, while Bax and cleaved-caspase3 were 
      increased. As key therapeutic measures, gene therapy, and magnetic hyperthermia 
      have shown a synergistic effect in this treatment strategy, with a combined index 
      (q index) of 1.23. CONCLUSION: In conclusion, we developed MUC1-C shRNA@Fe(3)O(4) 
      MNPs with magnetic hyperthermia and gene therapy functions, which have shown 
      satisfactory therapeutic effects on TNBC without significant side effects. This 
      study provides a potential option for the precision treatment of TNBC.
CI  - (c) 2023 Li et al.
FAU - Li, Zhifeng
AU  - Li Z
AUID- ORCID: 0000-0002-6141-5184
AD  - Medical School of Nantong University, Nantong, Jiangsu, People's Republic of 
      China.
AD  - Clinical Laboratory, Taizhou People's Hospital (Affiliated Hospital 5 of Nantong 
      University), Taizhou, Jiangsu, People's Republic of China.
FAU - Guo, Ting
AU  - Guo T
AD  - Research Center of Clinical Medicine, Taizhou People's Hospital (Affiliated 
      Hospital 5 of Nantong University), Taizhou, Jiangsu, People's Republic of China.
FAU - Zhao, Susu
AU  - Zhao S
AD  - Department of Pathology, Affiliated Hospital of Nanjing University of Chinese 
      Medicine, Nanjing, Jiangsu, People's Republic of China.
FAU - Lin, Mei
AU  - Lin M
AD  - Clinical Laboratory, Taizhou People's Hospital (Affiliated Hospital 5 of Nantong 
      University), Taizhou, Jiangsu, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20231006
PL  - New Zealand
TA  - Int J Nanomedicine
JT  - International journal of nanomedicine
JID - 101263847
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (Magnetite Nanoparticles)
RN  - 0 (MUC1 protein, human)
RN  - 0 (Mucin-1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Iron Compounds)
SB  - IM
MH  - Humans
MH  - bcl-2-Associated X Protein
MH  - Cell Line, Tumor
MH  - Hyperthermia, Induced
MH  - Magnetic Fields
MH  - *Magnetite Nanoparticles/therapeutic use
MH  - Mucin-1/genetics
MH  - NF-E2-Related Factor 2
MH  - *RNA, Small Interfering/genetics
MH  - *Triple Negative Breast Neoplasms/genetics/therapy
MH  - Iron Compounds
MH  - Magnetic Iron Oxide Nanoparticles
PMC - PMC10563812
OTO - NOTNLM
OT  - MUC1
OT  - ferroptosis
OT  - hyperthermia
OT  - nanoparticle
OT  - triple-negative breast cancer
COIS- The authors declare no conflicts of interest in this work.
EDAT- 2023/10/12 06:43
MHDA- 2023/10/13 06:45
PMCR- 2023/10/06
CRDT- 2023/10/12 04:16
PHST- 2023/07/27 00:00 [received]
PHST- 2023/09/25 00:00 [accepted]
PHST- 2023/10/13 06:45 [medline]
PHST- 2023/10/12 06:43 [pubmed]
PHST- 2023/10/12 04:16 [entrez]
PHST- 2023/10/06 00:00 [pmc-release]
AID - 426849 [pii]
AID - 10.2147/IJN.S426849 [doi]
PST - epublish
SO  - Int J Nanomedicine. 2023 Oct 6;18:5651-5670. doi: 10.2147/IJN.S426849. 
      eCollection 2023.