Abstract

Glioma is one of the deadliest intrinsic brain tumours due to its invasive growth. The effect of glioma treatment is poor because of the presence of the blood-brain barrier and blood tumour barrier and insufficient drug targeting. DNA tetrahedrons (TDN) show great potential for drug delivery and may be a novel therapeutic strategy for glioma. In this study, we used TDN to deliver doxorubicin (DOX) for the glioma therapy. Gint4.T, an aptamer that could recognize platelet-derived growth factor receptor β on tumour cell, was used to modify TDN (Apt-TDN) for targeted drug delivery. The TDN were self-assembled by one-step synthesis, which showed small size (10 nm) and negative charge. Fetal bovine serum test showed its stability as a drug delivery vehicle. Apt-TDN could be effectively taken up by U87MG cells. Compared with DOX and DOX@TDN (TDN loaded with DOX), the DOX@Apt-TDN (Gint4.T-modified TDN loaded with DOX) showed more early apoptosis rate, higher cell cycle arrest, and greater cytotoxicity towards U87MG cells. In conclusion, our findings indicated that DOX@Apt-TDN provides a novel therapy with promising clinical application for gliomas patients.

Highlights

  • Glioma, a tumour derived from the neuroepithelium, is the most common intracranial malignancy

  • Kafa et al [5] designed chemically functionalized multi-walled carbon nanotubes (f-MWNTs) targeting ANG and confirmed their ability to cross the blood-brain barrier (BBB) through in vivo and in vitro experiments. These nanomaterials may be distributed to various organs throughout the body or even enter the central nervous system (CNS), where they may cause neurotoxicity [6]

  • Synthesis and Characterization of the TDN and Gint4.T-modified TDN (Apt-TDN) The TDN was self-assembled from four oligonucleotides (Table 1) via single-step synthesis as previously reported [18, 29]

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Summary

Introduction

A tumour derived from the neuroepithelium, is the most common intracranial malignancy. Traditional chemotherapy for glioma does not show a good outcome due to poor tumour targeting, complications due to the blood-brain barrier (BBB) and blood tumour barrier (BTB), and insufficient drug targeting. Nanoparticles have emerged as the most promising drug-carrying tool Because of their size advantage, nanoparticles can cross the BBB and exert an antitumour effect. Kafa et al [5] designed chemically functionalized multi-walled carbon nanotubes (f-MWNTs) targeting ANG and confirmed their ability to cross the BBB through in vivo and in vitro experiments. These nanomaterials may be distributed to various organs throughout the body or even enter the central nervous system (CNS), where they may cause neurotoxicity [6]

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