GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy.
10.1016/j.apsb.2019.01.012
- Author:
Qin GUO
1
;
Chao LI
1
;
Wenxi ZHOU
1
;
Xinli CHEN
1
;
Yu ZHANG
1
;
Yifei LU
1
;
Yujie ZHANG
1
;
Qinjun CHEN
1
;
Donghui LIANG
1
;
Tao SUN
1
;
Chen JIANG
1
Author Information
1. Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
Cancer treatment;
Dehydroascorbic acid;
MiRNA21;
Nanomedicine;
RNAi nanoparticle;
Rolling circle transcription;
Self-assembly;
Tumor-targeting
- From:
Acta Pharmaceutica Sinica B
2019;9(4):832-842
- CountryChina
- Language:English
-
Abstract:
Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them. The purpose of this work is to construct a self-assembled glutathione (GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription (RCT) method. GSH-responsive cationic polymer polyethyleneimine (pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid (DHA), a targeting molecule, which is a substrate of glucose transporter 1 (GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.
