[Full text] Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA |

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Introduction

Glioma is the most malignant brain tumor that originates from glial cells. Besides, it is the most deadly type of brain tumor, with a five-year survival rate of less than 35%.1,2 The majority of glioma patients are treated with conventional surgery, combined with radiation, chemotherapy, or other drugs, due to the poor efficacy of traditional drug formulations.1,3 Although progressive therapy has been clinically used, scholars continue to explore more effective approaches to improve the survival rates of brain cancer patients.

One promising approach to glioma treatment is the inactivation of proteins critical to tumor survival or progression through RNA interference (RNAi), which ultimately results in the death of tumor cells. The main targets of RNAi therapy include oncogenes and genes involved in survival, anti-apoptosis, angiogenesis, metastasis, and chemotherapeutic resistance.4,5 Among the apoptotic inhibitor proteins, survivin has attracted increasing attention because of its high expression in tumor tissues and tumor cell lines.6 Survivin is also overexpressed in human gliomas, and its high protein expression level is associated with the degree of tumor malignancy.7–9 The higher expression level of survivin is also associated with a worse prognosis. Previous studies have shown that survivin-targeted RNA interference can inhibit cancer cell growth and prolong the survival of tumor-bearing mice.10 However, due to poor RNA stability, survivin cannot precisely enter tumor cells, thus, its application remains a challenge. Current RNA delivery methods include liposomes, cationic colloid, and carbon quantum dots, however, these methods have issues related to the material itself.5

Recently, a novel nanomaterial, DNA tetrahedron, has emerged as a multifunctional drug due to its anti-inflammatory, anti-oxidative, and neuroprotective effects.11 Besides, it has been used as a multifunctional drug carrier due to its high drug delivery capacity, good biocompatibility, and biodegradability.12 DNA nanomaterials are composed of only purines and pyrimidines, which means high editability. Therefore, a variety of tumor-targeting ligands and antitumor drugs are designed and modified on the tetrahedron. AS1411 is a guanine-rich DNA oligonucleotide produced by SELEX technology. It recognizes the nucleolin protein expressed on the tumor cell membrane through the high affinity of the guanine domain.13 Studies have shown that AS1411 inhibits the formation of new blood vessels and it is applied to ophthalmology and tumor-related diseases. Based on these facts, we modified aptamer AS1411 onto one side of the DNA tetrahedron to form a drug carrier with tumor-targeted function. Moreover, cy3 (a kind of anthocyanin dye), which emit red fluorescence under excitation, was attached to the DNA oligonucleotide. Based on the location of the fluorescence signal, the biological behavior of the nanomaterial in the cell can be determined.

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