Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma.
10.1016/j.apsb.2018.12.009
- Author:
Xi CAO
1
;
Ying HU
1
;
Shi LUO
1
;
Yuejing WANG
1
;
Tao GONG
1
;
Xun SUN
1
;
Yao FU
1
;
Zhirong ZHANG
1
Author Information
1. Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- Keywords:
5-FU, fluorouracil;
CLT, celastrol;
Celastrol;
DAPI, 4′,6-diamidino-2-phenylindole;
DiD, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate;
IKKα, IκB kinase α;
IKKβ, IκB kinase β;
IL-1β, interleukin 1 beta;
IL-6, interleukin 6;
Inflammation;
NF-κB, nuclear factor kappa B;
NIK, NF kappa B inducing kinase;
NNPs, neutrophil membrane-coated nanoparticles;
NPs, nanoparticles without neutrophil membrane coating;
Naïve neutrophils membrane;
PEG-PLGA nanoparticle;
PEG-PLGA, poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid);
PI, propidium iodide;
Pancreatic carcinoma;
TAK1, TGF-β-activated kinase 1;
TEM, transmission electronic microscopy;
TNF-α, tumor necrosis factor alpha
- From:
Acta Pharmaceutica Sinica B
2019;9(3):575-589
- CountryChina
- Language:English
-
Abstract:
Due to the critical correlation between inflammation and carcinogenesis, a therapeutic candidate with anti-inflammatory activity may find application in cancer therapy. Here, we report the therapeutic efficacy of celastrol as a promising candidate compound for treatment of pancreatic carcinoma naïve neutrophil membrane-coated poly(ethylene glycol) methyl ether--poly(lactic--glycolic acid) (PEG-PLGA) nanoparticles. Neutrophil membrane-coated nanoparticles (NNPs) are well demonstrated to overcome the blood pancreas barrier to achieve pancreas-specific drug delivery . Using tumor-bearing mice xenograft model, NNPs showed selective accumulations at the tumor site following systemic administration as compared to nanoparticles without neutrophil membrane coating. In both orthotopic and ectopic tumor models, celastrol-loaded NNPs demonstrated greatly enhanced tumor inhibition which significantly prolonged the survival of tumor bearing mice and minimizing liver metastases. Overall, these results suggest that celastrol-loaded NNPs represent a viable and effective treatment option for pancreatic carcinoma.
