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Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers

Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosp...

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Autores principales: Yang, Qiuxia, Peng, Yongbo, Deng, Zhengyu, Zhang, Dailiang, Long, Cheng-Yu, Zhang, Guo-Rong, Li, Juan, Wang, Xue-Qiang, Tan, Weihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508320/
https://www.ncbi.nlm.nih.gov/pubmed/37731726
http://dx.doi.org/10.1093/nsr/nwad113
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author Yang, Qiuxia
Peng, Yongbo
Deng, Zhengyu
Zhang, Dailiang
Long, Cheng-Yu
Zhang, Guo-Rong
Li, Juan
Wang, Xue-Qiang
Tan, Weihong
author_facet Yang, Qiuxia
Peng, Yongbo
Deng, Zhengyu
Zhang, Dailiang
Long, Cheng-Yu
Zhang, Guo-Rong
Li, Juan
Wang, Xue-Qiang
Tan, Weihong
author_sort Yang, Qiuxia
collection PubMed
description Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosphorothioate backbone modification strategy was applied to regulate the biomedical properties of pancreatic cancer cell–targeting aptamer for efficient in vivo drug delivery. Specifically, the CD71- targeting aptamer XQ-2d was modified into a fully thio-substituted aptamer S-XQ-2d, improving the plasma stability of S-XQ-2d and mitomycin C (MMC)-functionalized S-XQ-2d (MFSX), thus considerably prolonging their half-life in mice. Moreover, the binding and uptake capacities of S-XQ-2d were significantly enhanced. MFSX showed the same level of cytotoxicity as that of MMC against targeted cancer cells, but lower toxicity to non-targeted cells, highlighting its specificity and biosafety. Brief mechanistic studies demonstrated that XQ-2d and S-XQ-2d had different interaction modes and internalization pathways with the targeted cells.
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spelling pubmed-105083202023-09-20 Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers Yang, Qiuxia Peng, Yongbo Deng, Zhengyu Zhang, Dailiang Long, Cheng-Yu Zhang, Guo-Rong Li, Juan Wang, Xue-Qiang Tan, Weihong Natl Sci Rev Research Article Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosphorothioate backbone modification strategy was applied to regulate the biomedical properties of pancreatic cancer cell–targeting aptamer for efficient in vivo drug delivery. Specifically, the CD71- targeting aptamer XQ-2d was modified into a fully thio-substituted aptamer S-XQ-2d, improving the plasma stability of S-XQ-2d and mitomycin C (MMC)-functionalized S-XQ-2d (MFSX), thus considerably prolonging their half-life in mice. Moreover, the binding and uptake capacities of S-XQ-2d were significantly enhanced. MFSX showed the same level of cytotoxicity as that of MMC against targeted cancer cells, but lower toxicity to non-targeted cells, highlighting its specificity and biosafety. Brief mechanistic studies demonstrated that XQ-2d and S-XQ-2d had different interaction modes and internalization pathways with the targeted cells. Oxford University Press 2023-04-25 /pmc/articles/PMC10508320/ /pubmed/37731726 http://dx.doi.org/10.1093/nsr/nwad113 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yang, Qiuxia
Peng, Yongbo
Deng, Zhengyu
Zhang, Dailiang
Long, Cheng-Yu
Zhang, Guo-Rong
Li, Juan
Wang, Xue-Qiang
Tan, Weihong
Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers
title Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers
title_full Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers
title_fullStr Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers
title_full_unstemmed Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers
title_short Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers
title_sort regulating the properties of xq-2d for targeted delivery of therapeutic agents to pancreatic cancers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508320/
https://www.ncbi.nlm.nih.gov/pubmed/37731726
http://dx.doi.org/10.1093/nsr/nwad113
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