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Molecular domino reactor built by automated modular synthesis for cancer treatment
Yang,Yu1,2,4; He,Jiaxuan3; Zhu,Wenjun5; Pan,Xiaoshu4; Yazd,Hoda Safari4; Cui,Cheng3,4; Yang,Lu4; Li,Xiaowei4; Li,Long4; Cheng,Liang5; Feng,Liangzhu5; Wang,Ruowen1; Liu,Zhuang5; Chen,Meiwan2; Tan,Weihong1,3
Source PublicationTheranostics

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/heminpyrochlorophyll A, achieves in vivo photodynamic domino reaction for efficient cancer treatment by using a high concentration of hydrogen peroxide (H2O2) in the tumor microenvironment (TME) to produce O2, followed by consecutive generation of singlet oxygen (O2) using the pre-produced O2. 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 H2O2 to produce O2. This was followed by the generation of 1O2 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.

KeywordAutomated Modular Synthesis Molecular Domino Reactor Molecular “elements” Photodynamic Therapy Tumor Microenvironment (Tme)
URLView the original
Indexed BySCIE
WOS Research AreaResearch & Experimental Medicine
WOS SubjectMedicine, Research & Experimental
WOS IDWOS:000518773300014
Scopus ID2-s2.0-85081263488
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorChen,Meiwan; Tan,Weihong
Affiliation1.Institute of Molecular Medicine (IMM),Renji Hospital,State Key Laboratory of Oncogenes and Related Genes,Shanghai Jiao Tong University School of Medicine,College of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai,200240,China
2.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Taipa,Macao
3.Molecular Science and Biomedicine Laboratory (MBL),State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Chemistry and Chemical Engineering,College of Biology,Aptamer Engineering Center of Hunan Province,Hunan University,Changsha, Hunan,410082,China
4.Department of Chemistry,Department of Physiology and Functional Genomics,Center for Research at Bio/Nano Interface,Health Cancer Center,UF Genetics Institute,McKnight Brain Institute,University of Florida,Gainesville,32611-7200,United States
5.Institute of Functional Nano and Soft Materials Laboratory (FUNSOM),Soochow University,Suzhou, Jiangsu,215123,China
First Author AffilicationInstitute of Chinese Medical Sciences;  Cancer Centre
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yang,Yu,He,Jiaxuan,Zhu,Wenjun,et al. Molecular domino reactor built by automated modular synthesis for cancer treatment[J]. Theranostics,2020,10(9):4030-4041.
APA 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.(2020).Molecular domino reactor built by automated modular synthesis for cancer treatment.Theranostics,10(9),4030-4041.
MLA Yang,Yu,et al."Molecular domino reactor built by automated modular synthesis for cancer treatment".Theranostics 10.9(2020):4030-4041.
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