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A reconfigurable DNA framework nanotube-assisted antiangiogenic therapy for effective protection against multi-organ injury
  • +9
  • Wei Li,
  • Zhongliang Wang,
  • Qing Su,
  • Qian Wu,
  • Jie Chen,
  • Shuhan Zhu,
  • Xiaodie Li,
  • Hao Wei,
  • Jialin Zeng,
  • Linlang Guo,
  • Jian He,
  • Chao Zhang
Wei Li
Zhujiang Hospital of Southern Medical University
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Zhongliang Wang
Zhujiang Hospital of Southern Medical University
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Qing Su
Zhujiang Hospital of Southern Medical University
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Qian Wu
Peking University Sixth Hospital
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Jie Chen
Cancer Hospital of Shantou University Medical College
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Shuhan Zhu
Zhujiang Hospital of Southern Medical University
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Xiaodie Li
Zhujiang Hospital of Southern Medical University
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Hao Wei
The Affiliated Hospital of Qingdao University
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Jialin Zeng
Zhujiang Hospital of Southern Medical University
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Linlang Guo
Zhujiang Hospital of Southern Medical University
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Jian He
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital

Corresponding Author:[email protected]

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Chao Zhang
Zhujiang Hospital of Southern Medical University
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Abstract

With the burgeoning development of antiangiogenic therapy, various of antiangiogenic drugs have been developed and applied to cancer treatment. Nonetheless, for antiangiogenic drugs, the confined tumor targeting ability as well as the nonspecific bio-distribution often compromises the therapeutic outcome and causes serious multi-organ injury. In this study, we programme a reconfigurable DNA framework nanotube (rDFN) for manageable delivery of antiangiogenic drugs to minimize their damage to normal tissues. The fastened tubular structure of rDFN circumvented the direct expose of cargo endostar (Endo), a China Food and Drug Administration-approved antiangiogenic drug, to normal tissues. Meanwhile, the outside bedeck of rDFN with AS1411, a specific DNA aptamer for tumor-overexpressed nucleolin, conferred the encased Endo with greater tumor-targeting ability. Upon entry into tumor sites, nucleolin-responsive fasteners would be opened, allowing the controlled release of Endo. Based on the protective loading and activable unloading of Endo, an amplified anti-tumor effect and a reduced multi-organ injury were concurrently achieved. Conclusively, our work opens a new avenue for reducing antiangiogenic therapy-induced multi-organ injury.