Versatile cationic liposomes for RIP3 overexpression in colon cancer therapy and RIP3 downregulation in acute pancreatitis therapy

Abstract

Because the induction of strong host antitumor responses plays a very important role in antitumor therapy, identifying effective approaches to elicit immunogenic cell death could have important implications. RIP3-dependent necroptotic cancer cells have been reported to release damage-associated molecular patterns and enhance antitumor immunity. In this study, hyaluronic acid-conjugated cationic liposomes (DOTAP/DOPE/PEG-DSPE/CHOL) (HA-P-LP) were prepared as a vector for mRIP3-pDNA overexpression in tumours. Compared with standard cationic liposomes, this vector markedly increased cellular gene internalisation in vitro, enhanced the tumour-targeting effect in vivo and exhibited a significant antitumor effect in combination with adjuvant chloroquine. Considering the dramatic increase in RIP3 under the pathological condition of pancreatitis and the correlation between pancreatitis and necroptosis, non-HA-conjugated liposomes with the same formulation loaded with shRNA mRIP3-pDNA effectively controlled the disease by decreasing the serum amylase concentration and inflammatory cell infiltration. The versatile cationic liposomes loaded with plasmids with opposing functions in this study provide a new concept and method for both tumour therapy and pancreatitis therapy.

Keywords:

• RIP3 overexpression
• necroptosis
• RIP3 downregulation
• pancreatitis
• HA-P-LP

Acknowledgements

mRIP3-pDNA, Ctrl-pDNA, shRNA-RIP3-pDNA and Ctrl shRNA-pDNA were gifts from Dr Jiahuai Han (Key Laboratory of the Ministry of Education for Cell Biology and Tumour Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China).

Disclosure statement

The authors declare no competing financial interests.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81973268] and the China Postdoctoral Science Foundation [2014T70877 and 2013M542421].