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Controlled sequential in situ self-assembly and disassembly of a fluorogenic cisplatin prodrug for cancer theranostics

Author

Listed:
  • Xidan Wen

    (Nanjing University)

  • Rui Zhang

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Yuxuan Hu

    (Nanjing University)

  • Luyan Wu

    (Nanjing University)

  • He Bai

    (Nanjing University)

  • Dongfan Song

    (Nanjing University)

  • Yanfeng Wang

    (Nanjing University)

  • Ruibing An

    (Nanjing University)

  • Jianhui Weng

    (Nanjing University)

  • Shuren Zhang

    (Nanjing University)

  • Rong Wang

    (Nanjing University)

  • Ling Qiu

    (Jiangsu Institute of Nuclear Medicine)

  • Jianguo Lin

    (Jiangsu Institute of Nuclear Medicine)

  • Guandao Gao

    (Nanjing University)

  • Hong Liu

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Zijian Guo

    (Nanjing University)

  • Deju Ye

    (Nanjing University)

Abstract

Temporal control of delivery and release of drugs in tumors are important in improving therapeutic outcomes to patients. Here, we report a sequential stimuli-triggered in situ self-assembly and disassembly strategy to direct delivery and release of theranostic drugs in vivo. Using cisplatin as a model anticancer drug, we design a stimuli-responsive small-molecule cisplatin prodrug (P-CyPt), which undergoes extracellular alkaline phosphatase-triggered in situ self-assembly and succeeding intracellular glutathione-triggered disassembly process, allowing to enhance accumulation and elicit burst release of cisplatin in tumor cells. Compared with cisplatin, P-CyPt greatly improves antitumor efficacy while mitigates off-target toxicity in mice with subcutaneous HeLa tumors and orthotopic HepG2 liver tumors after systemic administration. Moreover, P-CyPt also produces activated near-infrared fluorescence (at 710 nm) and dual photoacoustic imaging signals (at 700 and 750 nm), permitting high sensitivity and spatial-resolution delineation of tumor foci and real-time monitoring of drug delivery and release in vivo. This strategy leverages the advantages offered by in situ self-assembly with those of intracellular disassembly, which may act as a general platform for the design of prodrugs capable of improving drug delivery for cancer theranostics.

Suggested Citation

  • Xidan Wen & Rui Zhang & Yuxuan Hu & Luyan Wu & He Bai & Dongfan Song & Yanfeng Wang & Ruibing An & Jianhui Weng & Shuren Zhang & Rong Wang & Ling Qiu & Jianguo Lin & Guandao Gao & Hong Liu & Zijian Gu, 2023. "Controlled sequential in situ self-assembly and disassembly of a fluorogenic cisplatin prodrug for cancer theranostics," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36469-1
    DOI: 10.1038/s41467-023-36469-1
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    References listed on IDEAS

    as
    1. Haoke Zhang & Xiaoyan Zheng & Ryan T. K. Kwok & Jia Wang & Nelson L. C. Leung & Lin Shi & Jing Zhi Sun & Zhiyong Tang & Jacky W. Y. Lam & Anjun Qin & Ben Zhong Tang, 2018. "In situ monitoring of molecular aggregation using circular dichroism," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    2. Han Ren & Xiang-Zhong Zeng & Xiao-Xiao Zhao & Da-yong Hou & Haodong Yao & Muhammad Yaseen & Lina Zhao & Wan-hai Xu & Hao Wang & Li-Li Li, 2022. "A bioactivated in vivo assembly nanotechnology fabricated NIR probe for small pancreatic tumor intraoperative imaging," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Yuan Gao & Junfeng Shi & Dan Yuan & Bing Xu, 2012. "Imaging enzyme-triggered self-assembly of small molecules inside live cells," Nature Communications, Nature, vol. 3(1), pages 1-8, January.
    4. Michael Jenkyn-Bedford & Morgan L. Jones & Yasemin Baris & Karim P. M. Labib & Giuseppe Cannone & Joseph T. P. Yeeles & Tom D. Deegan, 2021. "A conserved mechanism for regulating replisome disassembly in eukaryotes," Nature, Nature, vol. 600(7890), pages 743-747, December.
    5. Hong-Wei An & Li-Li Li & Yi Wang & Ziqi Wang & Dayong Hou & Yao-Xin Lin & Sheng-Lin Qiao & Man-Di Wang & Chao Yang & Yong Cong & Yang Ma & Xiao-Xiao Zhao & Qian Cai & Wen-Ting Chen & Chu-Qi Lu & Wanha, 2019. "A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
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