Volume 64, Issue 24 e202503004
Research Article

Spherical Nucleic Acids-Directed Cryosynthesis of Manganese Nanoagents for Tumor Imaging and Therapy

Wenjing Xie

Wenjing Xie

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 China

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049 China

These authors contributed equally to this work.

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Qiangjun Hao

Qiangjun Hao

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 China

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049 China

These authors contributed equally to this work.

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Zi Ye

Zi Ye

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 China

School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310013 China

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049 China

These authors contributed equally to this work.

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Rui Sha

Rui Sha

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 China

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049 China

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Bei Wen

Bei Wen

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 China

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049 China

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Hailin Wang

Hailin Wang

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 China

School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310013 China

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049 China

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Hongquan Zhang

Hongquan Zhang

Division of Analytical & Environmental Toxicology, Faculty of Medicine & Dentistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, T6G2G3 Canada

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Guohua Jia

Guohua Jia

School of Molecular and Life Sciences, Curtin University, Bentely, WA, 6102 Australia

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X. Chris Le

X. Chris Le

Division of Analytical & Environmental Toxicology, Faculty of Medicine & Dentistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, T6G2G3 Canada

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Guibin Jiang

Guibin Jiang

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 China

School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310013 China

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049 China

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Hanyong Peng

Corresponding Author

Hanyong Peng

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 China

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049 China

E-mail: [email protected]

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First published: 03 April 2025

Graphical Abstract

DNA-templated theranostic manganese nanoparticles synthesized under liquid nitrogen show features of magnetic resonance imaging, gene silencing, and chemodynamic therapy for tumors.

Abstract

DNAzyme-based theranostic nanotechnologies that can respond to specific tumor pathophysiological parameters hold great promise for tumor diagnostics and effective treatments. However, their clinical translation is hindered by insufficient intracellular availability of essential metal cofactors required for DNAzyme activation. To overcome this limitation, we developed a temperature-controlled synthesis strategy for fabricating multifunctional DNA-templated manganese carbonate nanoparticles (DtMnP). The process involves three critical phases: (i) spherical nucleic acid hybrids, DNAzyme-functionalized AuNPs, serve as scaffolds for spatially controlled Mn2+ deposition through phosphate coordination, initiating heterogeneous nucleation of MnCO3; (ii) rapid liquid nitrogen freezing induces nanoparticle growth along DNA templates; and (iii) lyophilization-mediated structural stabilization enables convenient long-term storage. The DtMnP exhibits pH-responsive dissolution, releasing 90% of Mn2+ within 60 min under tumor microenvironment conditions (pH 5.5). The released Mn2+ ion enables dual functionality: (i) superior magnetic resonance imaging (MRI) contrast of MCF-7 xenograft models with enhanced biosafety, and (ii) synergistic therapeutic efficacy through DNAzyme-mediated EGR-1 gene silencing (60% mRNA downregulation) combined with Mn2+-catalyzed Fenton reactions generating cytotoxic hydroxyl radicals (45% apoptosis in MCF-7 cells). The cryo-encapsulated DtMnP exemplifies a flexible and efficient approach for integrating various functional components into a single nanoparticle for tumor theranostic applications.

Conflict of Interests

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available in the Supporting Information of this article.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.