DataSheet1_Computable structured aptamer for targeted treatment of ovarian cancer.pdf

Nucleolin protein expression is higher on the ovarian cancer cell surface. AS1411, a DNA aptamer, can bind with nucleolin protein specifically. In this study, we developed HA and ST DNA tiles to assemble six AS1411 aptamers to deliver doxorubicin. In addition, to superior serum stability and drug loading, HA-6AS and ST-6AS outperformed TDN-AS in cellular uptake. HA-6AS and ST-6AS exhibited satisfactory targeted cytotoxicity and achieved resounding lysosomal escape. Moreover, when injected into nude mice subcutaneous xenograft models, HA-6AS reached the peak in tumor more quickly than ST-6AS, and better expressed the active targeting ability of AS1411. Our study suggests that designing appropriate DNA tiles to assemble different aptamers to deliver different chemotherapeutic drugs is a promising treatment for ovarian cancer.

卵巢癌细胞表面核仁蛋白的表达水平较高。AS1411，一种DNA适体，能够特异性地与核仁蛋白结合。在本研究中，我们开发了一种含有多聚赖氨酸（HA）和壳聚糖（ST）的DNA瓦片，用以组装六个AS1411适体，以便递送阿霉素。此外，鉴于其优异的血清稳定性和药物负载能力，HA-6AS和ST-6AS在细胞摄取方面超越了TDN-AS。HA-6AS和ST-6AS表现出令人满意的靶向细胞毒性，并实现了显著的溶酶体逃逸。更进一步，当注射入裸鼠皮下异种移植模型时，HA-6AS相较于ST-6AS，在肿瘤组织中更快地达到峰值，并更有效地表达了AS1411的活性靶向能力。本研究表明，通过设计合适的DNA瓦片来组装不同适体，以便递送不同的化疗药物，是一种有潜力的卵巢癌治疗方法。