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Self-reporting photodynamic nanobody conjugate for precise and sustainable large-volume tumor treatment

Author

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  • Yingchao Chen

    (Dalian University of Technology
    Liaoning Binhai Laboratory)

  • Tao Xiong

    (Dalian University of Technology
    Liaoning Binhai Laboratory)

  • Qiang Peng

    (Dalian University of Technology
    Liaoning Binhai Laboratory)

  • Jianjun Du

    (Dalian University of Technology
    Liaoning Binhai Laboratory)

  • Wen Sun

    (Dalian University of Technology
    Liaoning Binhai Laboratory)

  • Jiangli Fan

    (Dalian University of Technology
    Liaoning Binhai Laboratory)

  • Xiaojun Peng

    (Dalian University of Technology
    Liaoning Binhai Laboratory)

Abstract

Nanobodies (Nbs), the smallest antigen-binding fragments with high stability and affinity derived from the variable domain of naturally occurring heavy-chain-only antibodies in camelids, have been shown as an efficient way to improve the specificity to tumors for photodynamic therapy (PDT). Nonetheless, the rapid clearance of Nbs in vivo restricts the accumulation and retention of the photosensitizer at the tumor site causing insufficient therapeutic outcome, especially in large-volume tumors. Herein, we develop photodynamic conjugates, MNB-Pyra Nbs, through site-specific conjugation between 7D12 Nbs and type I photosensitizer MNB-Pyra (morpholine-modified nile blue structure connected to pyrazolinone) in a 1:2 ratio. The photosensitizers with long-term retention can be released at the tumor site by reactive oxygen species cleavage after illumination, accompanied with fluorescence recovery for self-reporting the occurrence of PDT. Ultimately, a single dose of MNB-Pyra Nbs demonstrate highly effective tumor suppression with high biosafety in the large-volume tumor models after three rounds of PDT. This nanobody conjugate provides a paradigm for the design of precise long-time retention photosensitizers and is expected to promote the development of PDT.

Suggested Citation

  • Yingchao Chen & Tao Xiong & Qiang Peng & Jianjun Du & Wen Sun & Jiangli Fan & Xiaojun Peng, 2024. "Self-reporting photodynamic nanobody conjugate for precise and sustainable large-volume tumor treatment," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51253-5
    DOI: 10.1038/s41467-024-51253-5
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    1. Dongdong Wang & Huihui Wu & Soo Zeng Fiona Phua & Guangbao Yang & Wei Qi Lim & Long Gu & Cheng Qian & Haibao Wang & Zhen Guo & Hongzhong Chen & Yanli Zhao, 2020. "Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Francesco Roncato & Fatlum Rruga & Elena Porcù & Elisabetta Casarin & Roberto Ronca & Federica Maccarinelli & Nicola Realdon & Giuseppe Basso & Ronen Alon & Giampietro Viola & Margherita Morpurgo, 2018. "Improvement and extension of anti-EGFR targeting in breast cancer therapy by integration with the Avidin-Nucleic-Acid-Nano-Assemblies," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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    1. Bowen Li & Jianwu Tian & Fu Zhang & Chongzhi Wu & Zhiyao Li & Dandan Wang & Jiahao Zhuang & Siqin Chen & Wentao Song & Yufu Tang & Yuan Ping & Bin Liu, 2024. "Self-assembled aldehyde dehydrogenase-activatable nano-prodrug for cancer stem cell-enriched tumor detection and treatment," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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