Cargando…
Molecular domino reactor built by automated modular synthesis for cancer treatment
Rationale: A cascade, or domino, reaction consists of two, or more, consecutive reactions such that subsequent reactions occur only if some chemical functionality has first been established in the prior step. However, while construction of predesigned and desired molecular domino reactors in a tailo...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086356/ https://www.ncbi.nlm.nih.gov/pubmed/32226537 http://dx.doi.org/10.7150/thno.43581 |
_version_ | 1783509110462873600 |
---|---|
author | Yang, Yu He, Jiaxuan Zhu, Wenjun Pan, Xiaoshu Yazd, Hoda Safari Cui, Cheng Yang, Lu Li, Xiaowei Li, Long Cheng, Liang Feng, Liangzhu Wang, Ruowen Liu, Zhuang Chen, Meiwan Tan, Weihong |
author_facet | Yang, Yu He, Jiaxuan Zhu, Wenjun Pan, Xiaoshu Yazd, Hoda Safari Cui, Cheng Yang, Lu Li, Xiaowei Li, Long Cheng, Liang Feng, Liangzhu Wang, Ruowen Liu, Zhuang Chen, Meiwan Tan, Weihong |
author_sort | Yang, Yu |
collection | PubMed |
description | Rationale: A cascade, or domino, reaction consists of two, or more, consecutive reactions such that subsequent reactions occur only if some chemical functionality has first been established in the prior step. However, while construction of predesigned and desired molecular domino reactors in a tailored manner is a valuable endeavor, it is still challenging. Methods: To address this challenge, we herein report an aptamer-based photodynamic domino reactor built through automated modular synthesis. The engineering of this reactor takes advantage of the well-established solid-phase synthesis platform to incorporate a photosensitizer into G-quadruplex/ hemin DNAzyme at the molecular level. Results: As a proof of concept, our photodynamic domino reactor, termed AS1411/hemin- pyrochlorophyll A, achieves in vivo photodynamic domino reaction for efficient cancer treatment by using a high concentration of hydrogen peroxide (H(2)O(2)) in the tumor microenvironment (TME) to produce O(2), followed by consecutive generation of singlet oxygen ((1)O(2)) using the pre-produced O(2). More specifically, phosphoramidite PA (pyrochlorophyll A) is coupled to aptamer AS1411 to form AS1411-PA ApDC able to simultaneously perform in vivo targeted imaging and photodynamic therapy (PDT). The insertion of hemin into the AS1411 G-quadruplex was demonstrated to alleviate tumor hypoxia by decomposition of H(2)O(2) to produce O(2). This was followed by the generation of (1)O(2) by PA to trigger cascading amplified PDT. Conclusion: Therefore, this study provides a general strategy for building an aptamer-based molecular domino reactor through automated modular synthesis. By proof of concept, we further demonstrate a novel method of achieving enhanced PDT, as well as alleviating TME hypoxia at the molecular level. |
format | Online Article Text |
id | pubmed-7086356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-70863562020-03-27 Molecular domino reactor built by automated modular synthesis for cancer treatment Yang, Yu He, Jiaxuan Zhu, Wenjun Pan, Xiaoshu Yazd, Hoda Safari Cui, Cheng Yang, Lu Li, Xiaowei Li, Long Cheng, Liang Feng, Liangzhu Wang, Ruowen Liu, Zhuang Chen, Meiwan Tan, Weihong Theranostics Research Paper Rationale: A cascade, or domino, reaction consists of two, or more, consecutive reactions such that subsequent reactions occur only if some chemical functionality has first been established in the prior step. However, while construction of predesigned and desired molecular domino reactors in a tailored manner is a valuable endeavor, it is still challenging. Methods: To address this challenge, we herein report an aptamer-based photodynamic domino reactor built through automated modular synthesis. The engineering of this reactor takes advantage of the well-established solid-phase synthesis platform to incorporate a photosensitizer into G-quadruplex/ hemin DNAzyme at the molecular level. Results: As a proof of concept, our photodynamic domino reactor, termed AS1411/hemin- pyrochlorophyll A, achieves in vivo photodynamic domino reaction for efficient cancer treatment by using a high concentration of hydrogen peroxide (H(2)O(2)) in the tumor microenvironment (TME) to produce O(2), followed by consecutive generation of singlet oxygen ((1)O(2)) using the pre-produced O(2). More specifically, phosphoramidite PA (pyrochlorophyll A) is coupled to aptamer AS1411 to form AS1411-PA ApDC able to simultaneously perform in vivo targeted imaging and photodynamic therapy (PDT). The insertion of hemin into the AS1411 G-quadruplex was demonstrated to alleviate tumor hypoxia by decomposition of H(2)O(2) to produce O(2). This was followed by the generation of (1)O(2) by PA to trigger cascading amplified PDT. Conclusion: Therefore, this study provides a general strategy for building an aptamer-based molecular domino reactor through automated modular synthesis. By proof of concept, we further demonstrate a novel method of achieving enhanced PDT, as well as alleviating TME hypoxia at the molecular level. Ivyspring International Publisher 2020-03-04 /pmc/articles/PMC7086356/ /pubmed/32226537 http://dx.doi.org/10.7150/thno.43581 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Yang, Yu He, Jiaxuan Zhu, Wenjun Pan, Xiaoshu Yazd, Hoda Safari Cui, Cheng Yang, Lu Li, Xiaowei Li, Long Cheng, Liang Feng, Liangzhu Wang, Ruowen Liu, Zhuang Chen, Meiwan Tan, Weihong Molecular domino reactor built by automated modular synthesis for cancer treatment |
title | Molecular domino reactor built by automated modular synthesis for cancer treatment |
title_full | Molecular domino reactor built by automated modular synthesis for cancer treatment |
title_fullStr | Molecular domino reactor built by automated modular synthesis for cancer treatment |
title_full_unstemmed | Molecular domino reactor built by automated modular synthesis for cancer treatment |
title_short | Molecular domino reactor built by automated modular synthesis for cancer treatment |
title_sort | molecular domino reactor built by automated modular synthesis for cancer treatment |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086356/ https://www.ncbi.nlm.nih.gov/pubmed/32226537 http://dx.doi.org/10.7150/thno.43581 |
work_keys_str_mv | AT yangyu moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT hejiaxuan moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT zhuwenjun moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT panxiaoshu moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT yazdhodasafari moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT cuicheng moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT yanglu moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT lixiaowei moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT lilong moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT chengliang moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT fengliangzhu moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT wangruowen moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT liuzhuang moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT chenmeiwan moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment AT tanweihong moleculardominoreactorbuiltbyautomatedmodularsynthesisforcancertreatment |