Researchers from Xi'an Jiaotong University have constructed two spherical nucleic acids, SNA1 and SNA2/DOX, using two antisense oligonucleotides that can complement oncogenic miRNAs to modify gold nanoparticles to effectively manipulate the genetic environment for gene therapy.

A team led by Professor Chen Xin from the School of Chemical Engineering and Technology and a team led by Professor Zhang Yanmin from the School of Pharmacy modified gold nanoparticles with two antisense oligonucleotides that can complement oncogenic miRNAs, and further linked the antitumor drug doxorubicin to the antisense nucleotide chain through hybridization.

The miR-21 was able to induce cross-linking of two antisense nucleotides while being captured, resulting in the aggregation of spherical nucleic acids. This process not only enables the in situ generation of photothermal reagents (aggregated gold nanoparticles) in cells to achieve precise photothermal therapy.

Moreover, due to the significant increase in the size of SNAs after aggregation, their residence time in tumor cells is prolonged, which effectively improves the cycle and efficiency of gene therapy and photothermal therapy.

In addition, miR-155 can trigger the release of doxorubicin while being captured, thereby providing precision chemotherapy with high tumor selectivity.

The results of in vivo and in vitro experiments show that this combined strategy of gene therapy, photothermal therapy, and chemotherapy triggered by oncogenic miRNAs can not only effectively inhibit tumor growth and migration, but is also less toxic and has fewer side effects. It is expected to be more widely used in tumor therapy.

Schematic diagram of the structure and therapeutic mechanism of spherical nucleic acid

The results were published in Advanced Materials under the title Intelligent Gold Nanoparticles with Oncogenic MicroRNA-dependent Activities to Manipulate Tumorigenic Environments for Synergistic Tumor Therapy. (Link to the paper: https://doi.org/10.1002/adma.202110219)

Dr Wang Xiangdong from School of Chemical Engineering and Technology and Dr Yang Tianfeng from School of Pharmacy are the co-first authors. Professor Chen and Professor Zhang are the co-corresponding authors. The research was financed by the National Natural Science Foundation of China.

Oncogenic miRNAs such as MiR-21 and miR-155 are significantly expressed in a variety of malignant tumors, and are closely related to tumor proliferation, differentiation and migration.

Studies have shown that reducing the level of oncogenic miRNAs in tumor cells can effectively inhibit their proliferation and migration. Therefore, a series of nanomaterials that can capture different oncogenic miRNAs have been developed one after another, and to a certain extent, the treatment of colon cancer, breast cancer, liver cancer and other malignant tumors has been realized by inhibiting the corresponding miRNAs.