Volume 17, Issue 51 2104722
Research Article

Photoactivated Self-Disassembly of Multifunctional DNA Nanoflower Enables Amplified Autophagy Suppression for Low-Dose Photodynamic Therapy

Jinjin Shi

Jinjin Shi

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

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Danyu Wang

Danyu Wang

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

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Yanrui Ma

Yanrui Ma

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

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Jingwen Liu

Jingwen Liu

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

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Yanan Li

Yanan Li

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

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Rashed Reza

Rashed Reza

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

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Zhenzhong Zhang

Zhenzhong Zhang

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

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Junjie Liu

Corresponding Author

Junjie Liu

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

E-mail: [email protected], [email protected]

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Kaixiang Zhang

Corresponding Author

Kaixiang Zhang

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou, 450001 China

E-mail: [email protected], [email protected]

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First published: 20 October 2021
Citations: 21

Abstract

Low-dose photodynamic therapy (PDT) holds great promise for reducing undesired patient photosensitivity in cancer treatment. Yet, its therapeutic effect is significantly affected by intracellular cytoprotective processes, such as autophagy. Here, an efficient autophagy suppressor is developed, which is a multifunctional DNA nanoflower (DNF) consisted of tumor-targeting aptamers and DNAzymes for silencing autophagy-related genes, with surface modification of low-dose photosensitizer (Ce6). It is found that the multifunctional DNF can specifically target tumor cells and generate reactive oxygen species (ROS) under light irradiation to trigger self-disassembly of DNF, enhancing the bioavailability of encoded DNAzymes, leading to amplified autophagy suppression. As a facile spatiotemporally programmable photogene therapy platform, the designed DNF is able to suppress tumor growth in vivo with a very low injection dose of Ce6 (18 µg kg−1, around 100 times lower than the generally applied dose), representing a promising strategy for cancer therapy with safely low-dose PDT.

Conflict of Interest

The authors declare no conflict of interest.

Data Availability Statement

Research data are not shared.

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