GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy

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.

MicroRNA‑375 prevents TGF‑β‑dependent transdifferentiation of lung fibroblasts via the MAP2K6/P38 pathway

“…Total RNA was extracted from the cultured cells using TRIzol ® reagent (Invitrogen; Thermo Fisher Scientific, Inc.), according to the manufacturer's instructions, and was then reverse transcribed to cDNA using the High-Capacity cDNA Reverse Transcription kit (Applied Biosystems; Thermo Fisher Scientific, Inc.), as previously described ( 35 , 36 ). The expression levels of fibrotic markers, collagen type I α1 ( Col1α1 ), Col3α1, Ctgf and fibronectin ( Fn ) were quantified with SYBR ® Premix EX Taq™ (Takara Biotechnology Co., Ltd.) and normalized to GAPDH .…”

Innovations in Biomaterial Design toward Successful RNA Interference Therapy for Cancer Treatment

“…[ 102 ] A recent study that exploited this approach was exploring the efficacy of what the authors referred to as GLUT‐1 targeted “nanopompons” delivering anti‐miR21 in the treatment of breast cancer. [ 90 ] About half a million tandem copies of anti‐miR21 were constructed into a nanoball using rolling circle transcription technology. [ 105 ]…”

The Role of Exosomal microRNA in Cancer Drug Resistance

“…The GLUT family is closely related to glucose transport into cells. GLUT1, one of the family members in GLUT, is upregulated in many malignant tumors (135). The upregulation of GLUT1 is associated with mammalian target of rapamycin (mTOR) and the activation of mTOR increases glycolysis and promotes drug resistance (132).…”