Automated screening of primary cell-based aptamers for targeting and therapy of pancreatic cancer

• Published in: Chinese chemical letters 2024-02, Vol.35 (2), p.108528, Article 108528
• Main Authors: Guo, Zhukang, Jin, Baijiang, Fang, Yile, Jin, Lian, Li, Song, Deng, Yan, Chen, Zhu, Chen, Hui, Zhang, Yuanying, Usman, Rabia, He, Nongyue
• Format: Article
• Language: English
• Subjects: Aptamer Cell-SELEX Automatic instrument Combination therapy Pancreatic cancer
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2023.108528

Although it has been developed for many years, nucleic acid aptamer screening technology still fails to be widely used, a considerable part of it is due to the variability of tumor cell morphology, which leads to the use of immortalized cell lines in the laboratory to screen nucleic acid aptamers for recognition ability of tumor cells in the diseased body. To address this, primary cells that can be stably passaged were isolated and extracted from spontaneous tumors of genetically engineered pancreatic ductal adenocarcinoma model mice in this study. Next, an automated screening instrument for nucleic acid aptamers developed autonomously by our group was used to perform efficient aptamer screening using a limited number of cells, and the obtained nucleic acid aptamers were affinity verified at the cellular level. Finally, to answer the question of the cell growth environment difference on the recognition ability of nucleic acid aptamers, we verified its targeting ability to tumors in vivo on a nude mice xenograft tumor model, and further used a common antitumor drug doxorubicin combined with nucleic acid aptamers to verify the drug loading ability of this aptamer combined with the targeting therapeutic ability. In this article, we realized primary cell-based nucleic acid aptamer screening through extraction and expansion form primary pancreatic cancer mouse. Using the results of the screening, specific recognition of pancreatic cancer cells was achieved on a laboratory cell line as well as on a cell derived xenograft (CDX). Moreover, we accomplished targeted drug delivery and treatment in nude mice with pancreatic cancer, which provided new ideas for the practical application of nucleic acid aptamers. [Display omitted]