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

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. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

This study isolated primary cells that can be stably passaged from spontaneous tumors of genetically engineered pancreatic ductal adenocarcinoma model mice and used an autonomously developed automated screening instrument for efficient nucleic acid aptamer screening. The obtained aptamers were affinity verified at the cellular level. The study also investigated the impact of cell growth environment difference on the recognition ability of aptamers and confirmed the targeting ability and drug loading ability of the aptamer.