Simultaneous Down-Regulation of Intracellular MicroRNA-21 and hTERT mRNA Using AS1411-Functionallized Gold Nanoprobes to Achieve Targeted Anti-Tumor Therapy

Abstract

Telomerase presents over-expression in most cancer cells and has been used as a near-universal marker of cancer. Studies have revealed that inhibiting telomerase activity by utilizing oligonucleotides to down-regulate the expression of intracellular human telomerase reverse-transcriptase (hTERT) mRNA is an effective method of achieving anti-tumor therapy. Considering that oncogenic microRNA-21 has been proven to indirectly up-regulate hTERT expression and drive cancer metastasis and aggression through increased telomerase activity, here, we constructed an AS1411-functionallized oligonucleotide-conjugated gold nanoprobe (Au nanoprobe) to simultaneously down-regulate intracellular microRNA-21 and hTERT mRNA by using anti-sense oligonucleotide technology to explore their targeted anti-tumor therapy effect. In vitro cell studies demonstrated that Au nanoprobes could effectively induce apoptosis and inhibit the proliferation of cancer cells by down-regulating intracellular hTERT activity. In vivo imaging and anti-tumor studies revealed that Au nanoprobes could accumulate at the tumor site and inhibit the growth of MCF-7 tumor xenografted on balb/c nude mice, thus having potential for anti-tumor therapy.

Keywords

• gene regulation
• microRNA-21
• hTERT mRNA
• gold nanoparticles
• anti-tumor