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Nano Research

Article Title

In vitro studies of polyethyleneimine coated miRNA microspheres as anticancer agents

Keywords

nanospheres, gene silencing, gene delivery, polyethylenimine, anticancer agents

Abstract

RNA plays important roles as a gene-silencing agent, a therapeutic agent forclinical treatment, and in the differentiation, proliferation, and development ofcells. However, RNA is very difficult to work with due to its sensitivity andfragility. Another obstacle in using RNA for gene delivery/silencing is its negativecharge, which causes its repulsion by cell membranes, which are also negativelycharged. Our recent study showed that miR-125b is upregulated in glioblastoma(GMB) and plays an oncogenic role in GMB cells by promoting cell proliferationand inhibiting apoptosis. Endogenous miR-125b can be blocked by transfectionof its antisense RNA molecule, miR-125b antisense (miR-125b-AS). Thus, miR-125b-AS can be developed as an RNA-based agent for cancer treatment. However,instability during storage and difficulty in delivery into cells has limited the useof RNA-based therapies thus far. In the current work, we demonstrate a shortand simple one-step technique for the preparation of positively charged RNAnanospheres (miR-125b-RNS and miR-125b-AS-RNS) coated with a bioavailablepolymer, polyethylenimine (PEI). These RNA nanospheres are able to penetratethe cell directly without the use of liposomes. Our study confirmed thatconverting miR-125b and miR-125b-AS into nanospheres is a viable approachfor storing RNA. In addition, this study provides evidence that PEI-coated RNAnanospheres have the potential to be used as a novel class of anticancer agents.

Graphical Abstract

Publisher

Tsinghua University Press

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