Research Institute of Sciences and New Technology , Mashhad 91778-99191 , Iran.
Mol Pharm. 2018 May 7;15(5):1972-1978. doi: 10.1021/acs.molpharmaceut.8b00124. Epub 2018 Apr 23.
Active targeting of nanostructures containing chemotherapeutic agents can improve cancer treatment. Here, a three-way junction pocket DNA nanostructure was developed for efficient doxorubicin (Dox) delivery into cancer cells. The three-way junction pocket DNA nanostructure is composed of three strands of AS1411 aptamer as both a therapeutic aptamer and nucleolin target, the potential biomarker of prostate (PC-3 cells) and breast (4T1 cells) cancers. The properties of the Dox-loaded three-way junction pocket DNA nanostructure were characterized and verified to have several advantages, including high serum stability and a pH-responsive property. Cellular uptake studies showed that the Dox-loaded DNA nanostructure was preferably internalized into target cancer cells (PC-3 and 4T1 cells). MTT cell viability assay demonstrated that the Dox-loaded DNA nanostructure had significantly higher cytotoxicity for PC-3 and 4T1 cells compared to that of nontarget cells (CHO cells, Chinese hamster ovary cell). The in vivo antitumor effect showed that the Dox-loaded DNA nanostructure was more effective in prohibition of the tumor growth compared to free Dox. These findings showed that the Dox-loaded three-way junction pocket DNA nanostructure could significantly reduce the cytotoxic effects of Dox against nontarget cells.
主动靶向含有化疗药物的纳米结构可以改善癌症治疗。在这里，开发了一种三链结口袋 DNA 纳米结构，用于将阿霉素（Dox）高效递送至癌细胞。三链结口袋 DNA 纳米结构由三条 AS1411 适体组成，作为治疗适体和核仁素的靶标，核仁素是前列腺（PC-3 细胞）和乳腺癌（4T1 细胞）的潜在生物标志物。负载 Dox 的三链结口袋 DNA 纳米结构的性质进行了表征和验证，具有几个优点，包括高血清稳定性和 pH 响应性。细胞摄取研究表明，负载 Dox 的 DNA 纳米结构更优先被靶癌细胞（PC-3 和 4T1 细胞）内化。MTT 细胞活力测定表明，负载 Dox 的 DNA 纳米结构对 PC-3 和 4T1 细胞的细胞毒性明显高于非靶细胞（CHO 细胞，中国仓鼠卵巢细胞）。体内抗肿瘤作用表明，与游离 Dox 相比，负载 Dox 的 DNA 纳米结构更能有效抑制肿瘤生长。这些发现表明，负载 Dox 的三链结口袋 DNA 纳米结构可以显著降低 Dox 对非靶细胞的细胞毒性作用。
