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.

核仁素（nucleolin）蛋白在卵巢癌细胞表面的表达水平更高。AS1411作为一种DNA适配体（DNA aptamer），可特异性结合核仁素蛋白。本研究中，我们构建了HA与ST型DNA瓦片（DNA tiles），通过其组装六条AS1411适配体以递送多柔比星（doxorubicin）。此外，凭借更优异的血清稳定性与药物负载性能，HA-6AS与ST-6AS在细胞摄取效果上优于TDN-AS。HA-6AS与ST-6AS展现出令人满意的靶向细胞毒性，并实现了高效的溶酶体逃逸。当将制剂注射至裸鼠皮下异种移植瘤模型中时，HA-6AS相较于ST-6AS可更快在肿瘤部位达到峰值浓度，更充分地展现了AS1411的主动靶向能力。本研究表明，设计适配的DNA瓦片以组装不同适配体来递送不同化疗药物，是一种颇具前景的卵巢癌治疗策略。