Ji Qinghong, Yang Qiangqiang, Ou Mengyao, Hong Min
School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China.
Nanomaterials (Basel). 2024 Dec 5;14(23):1956. doi: 10.3390/nano14231956.
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.
端粒酶在大多数癌细胞中呈现过表达，并且已被用作癌症的一种近乎通用的标志物。研究表明，利用寡核苷酸抑制端粒酶活性以下调细胞内人端粒酶逆转录酶（hTERT）mRNA的表达是实现抗肿瘤治疗的一种有效方法。鉴于致癌性微小RNA-21已被证明可通过增加端粒酶活性间接上调hTERT表达并驱动癌症转移和侵袭，在此，我们构建了一种AS1411功能化的寡核苷酸缀合金纳米探针（金纳米探针），通过反义寡核苷酸技术同时下调细胞内微小RNA-21和hTERT mRNA，以探索其靶向抗肿瘤治疗效果。体外细胞研究表明，金纳米探针可通过下调细胞内hTERT活性有效诱导癌细胞凋亡并抑制其增殖。体内成像和抗肿瘤研究表明，金纳米探针可在肿瘤部位积聚，并抑制接种于balb/c裸鼠的MCF-7肿瘤异种移植物的生长，因此具有抗肿瘤治疗潜力。
