GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy

Acta Pharmaceutica Sinica. B
Qin GuoChen Jiang

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...Continue Reading

Citations

Apr 23, 2020·Frontiers in Oncology·Qiao-Ru GuoJian-Ye Zhang
Jul 28, 2020·Advanced Drug Delivery Reviews·Fangli MoWeihong Tan
May 12, 2021·Advanced Healthcare Materials·Deidra M WardNicholas A Peppas

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Methods Mentioned

BETA
xenograft
dynamic light scattering
electrophoresis
flow cytometry
Protein Assay
fluorescence imaging
PCR

Software Mentioned

Zeta PALS
GraphPad Prism
GraphPad

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