Citation: Teng Wu, Min Tan, Heng-Ye Gong, Yong Wang, Xin-Tao Shuai. Co-delivery of Andrographolide and Notch1-targeted siRNA to Macrophages with Polymer-based Nanocarrier for Enhanced Anti-inflammation[J]. Chinese Journal of Polymer Science, ;2018, 36(12): 1312-1320. doi: 10.1007/s10118-018-2158-z shu

Co-delivery of Andrographolide and Notch1-targeted siRNA to Macrophages with Polymer-based Nanocarrier for Enhanced Anti-inflammation

Teng Wu ^1,2 ,
Min Tan ¹ ,
Heng-Ye Gong ¹ ,
Yong Wang ¹ ,
Xin-Tao Shuai ^1,2,,

a.
PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China
b.
Center of Biomedical Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China

Corresponding author: Xin-Tao Shuai, shuaixt@mail.sysu.edu.cn
Received Date: 25 April 2018
Revised Date: 9 May 2018
Accepted Date: 10 May 2018
Available Online: 22 June 2018

Chronic inflammatory responses induced by macrophages play a pivotal role in the progression of atherosclerosis. In the present study, a multifunctional nanocarrier based on poly(ethylene glycol)-block-poly(L-aspartic acid) grafted with diethylenetriamine, lysine and cholic acid (PEG-PAsp(DETA)-Lys-CA₂) polymer was synthesized for co-delivery of andrographolide and siRNA targeting Notch1 gene to alleviate the inflammatory response in macrophages. The nanocarrier exerted low cytotoxicity as well as high performance in drug/siRNA co-delivery. In vitro studies demonstrated the co-delivery of andrographolide and Notch1 siRNA not only significantly inhibited lipopolysaccharide (LPS)-activated interleukin-6 (IL-6) and monocytes chemotactic protein 1 (MCP-1) expression as well as blocked nuclear factor-κB (NF-κB) signal activation, but also interfered the Notch1 gene expression and increased anti-inflammatory cytokines such as interleukin-10 (IL-10) and arginase-1 expression obviously in macrophages. These results suggested that the combination therapy based on Notch1 siRNA and andrographolide co-delivered nanocarrier, i.e. suppressing the expression of pro-inflammatory cytokines while simultaneously increasing anti-inflammatory factors expression, be a feasible strategy for atherosclerosis treatment.
- Macrophages,
- Anti-inflamatory,
- Andrographolide,
- Notch1 siRNA
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