PMID- 32272830
OWN - NLM
STAT- MEDLINE
DCOM- 20231120
LR  - 20231120
IS  - 1827-1669 (Electronic)
IS  - 0026-4806 (Linking)
VI  - 114
IP  - 5
DP  - 2023 Oct
TI  - M1 macrophage-derived exosome-encapsulated cisplatin can enhance its anti-lung 
      cancer effect.
PG  - 634-641
LID - 10.23736/S0026-4806.20.06564-7 [doi]
AB  - BACKGROUND: The aim of this study was to study the efficacy of cisplatin-loaded 
      M1 macrophage secreted-exosomes (DDP-M1-Exos) in enhancing DDP antitumor effect. 
      METHODS: M1-Exos were first extracted using density gradient centrifugation, and 
      the DDP-M1-Exos system was established via electroporation. Then, the morphology, 
      particle size and maker proteins of the DDP-M1-Exos system were assessed using 
      transmission electron microscope, DLS and Western blotting (WB), respectively. 
      The uptake of Exos by mouse Lewis lung cancer (LLC) cells was observed under a 
      confocal laser scanning microscope, and the influence of the DDP-M1-Exos system 
      on the viability of Lewis cells was determined using methyl thiazolyl tetrazolium 
      assay and 4',6-diamidino-2-phenylindole staining. Besides, its impacts on the 
      messenger ribonucleic acid (mRNA) levels and protein expression levels of B-cell 
      lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and Caspase-3 in LLC cells 
      were examined using quantitative real-time PCR (qRT-PCR) and WB, respectively. 
      Finally, with the LLC-bearing mouse model as the object of study, the efficacy 
      was evaluated using terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) and hematoxylin-eosin staining staining in vivo. RESULTS: 
      Saucer-shaped Exos with a bilayer membrane, uniform particle size and highly 
      expressed CD81, Alix and HSP70 were successfully isolated from M1 macrophages via 
      density gradient centrifugation, and they were absorbed by LLC cells. Meanwhile, 
      the DDP-M1-Exos drug delivery system was successfully prepared using 
      electroporation technique. Compared with Control group, DDP and DDP-M1-Exos 
      groups exhibited a decrease in the proliferation rate of mouse LLC cells and an 
      increase in their apoptosis rate (*P<0.05), and the apoptosis rate in DDP-M1-Exos 
      group was substantially higher than that in DDP group ((#)P<0.01). According to 
      the qRT-PCR and WB results, DDP-M1-Exos up-regulated Bax and Caspase-3 in the 
      apoptosis signaling pathway to induce tumor cell apoptosis, thereby resisting 
      tumors. Moreover, through in-vivo experiments, it was found that M1-Exos alone 
      had a potential to suppress tumor growth, and that the carrier of M1-Exos could 
      not only kill tumor cells, but also encapsulate DDP to enhance its anti-lung 
      cancer effect. CONCLUSIONS: The DDP-M1-Exos drug delivery system is prepared 
      using Exos extracted via density gradient centrifugation by electroporation, and 
      the drug-loaded Exos are able to effectively inhibit the proliferation of tumor 
      cells and induce their apoptosis, exerting an antitumor effect.
FAU - Li, Jun
AU  - Li J
AD  - Department of Hematology and Oncology, China-Japan Union Hospital of Jinlin 
      University, Changchun, China.
FAU - Li, Ning
AU  - Li N
AD  - Department of Respiratory Medicine, China-Japan Union Hospital of Jinlin 
      University, Changchun, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Respiratory Medicine, China-Japan Union Hospital of Jinlin 
      University, Changchun, China - wangjing67@sina.com.cn.
LA  - eng
PT  - Journal Article
DEP - 20200408
PL  - Italy
TA  - Minerva Med
JT  - Minerva medica
JID - 0400732
RN  - Q20Q21Q62J (Cisplatin)
RN  - EC 3.4.22.- (Caspase 3)
RN  - 0 (bcl-2-Associated X Protein)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Cisplatin/pharmacology/therapeutic use
MH  - Caspase 3/metabolism
MH  - *Exosomes/genetics
MH  - bcl-2-Associated X Protein/metabolism
MH  - *Lung Neoplasms/drug therapy/metabolism
MH  - Apoptosis
MH  - Macrophages/metabolism
MH  - Cell Proliferation
EDAT- 2020/04/11 06:00
MHDA- 2023/11/20 06:55
CRDT- 2020/04/11 06:00
PHST- 2023/11/20 06:55 [medline]
PHST- 2020/04/11 06:00 [pubmed]
PHST- 2020/04/11 06:00 [entrez]
AID - S0026-4806.20.06564-7 [pii]
AID - 10.23736/S0026-4806.20.06564-7 [doi]
PST - ppublish
SO  - Minerva Med. 2023 Oct;114(5):634-641. doi: 10.23736/S0026-4806.20.06564-7. Epub 
      2020 Apr 8.