Original articles
Xi Cao, Ying Hu, Shi Luo, Yuejing Wang, Tao Gong, Xun Sun, Yao Fu, Zhirong Zhang. Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma[J]. Acta Pharmaceutica Sinica B, 2019, 9(3): 575-589

Neutrophil-mimicking therapeutic nanoparticles for targeted chemotherapy of pancreatic carcinoma
Xi Cao, Ying Hu, Shi Luo, Yuejing Wang, Tao Gong, Xun Sun, Yao Fu, Zhirong Zhang
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
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 via naïve neutrophil membrane-coated poly(ethylene glycol) methyl ether-block-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles. Neutrophil membranecoated nanoparticles (NNPs) are well demonstrated to overcome the blood pancreas barrier to achieve pancreas-specific drug delivery in vivo. 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.
Key words:    Naïve neutrophils membrane    Celastrol    PEG-PLGA nanoparticle    Pancreatic carcinoma    Inflammation   
Received: 2018-09-16     Revised:
DOI: 10.1016/j.apsb.2018.12.009
Funds: The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (81690261), Sichuan University Fund for Excellent Young Scholars (2017SCU04A23, China) and Sichuan Youth Science and Technology Innovation Research Team Funding (2016TD0001, China).
Corresponding author: Yao Fu, Zhirong Zhang     Email:yfu4@scu.edu.cn;zrzzl@vip.sina.com
Author description:
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Xi Cao
Ying Hu
Shi Luo
Yuejing Wang
Tao Gong
Xun Sun
Yao Fu
Zhirong Zhang

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