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Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy

Author

Listed:
  • Qingqing Yin

    (Peking University
    Peking University)

  • Anni Pan

    (Peking University)

  • Binlong Chen

    (Peking University)

  • Zenghui Wang

    (Peking University)

  • Mingmei Tang

    (Peking University)

  • Yue Yan

    (Peking University)

  • Yaoqi Wang

    (Peking University)

  • Heming Xia

    (Peking University)

  • Wei Chen

    (Peking University)

  • Hongliang Du

    (Peking University)

  • Meifang Chen

    (Peking University)

  • Chuanxun Fu

    (Peking University)

  • Yanni Wang

    (Peking University Cancer Hospital and Institute)

  • Xia Yuan

    (Peking University)

  • Zhihao Lu

    (Peking University Cancer Hospital and Institute)

  • Qiang Zhang

    (Peking University
    Peking University)

  • Yiguang Wang

    (Peking University
    Peking University)

Abstract

Nanoparticle internalisation is crucial for the precise delivery of drug/genes to its intracellular targets. Conventional quantification strategies can provide the overall profiling of nanoparticle biodistribution, but fail to unambiguously differentiate the intracellularly bioavailable particles from those in tumour intravascular and extracellular microenvironment. Herein, we develop a binary ratiometric nanoreporter (BiRN) that can specifically convert subtle pH variations involved in the endocytic events into digitised signal output, enabling the accurately quantifying of cellular internalisation without introducing extracellular contributions. Using BiRN technology, we find only 10.7–28.2% of accumulated nanoparticles are internalised into intracellular compartments with high heterogeneity within and between different tumour types. We demonstrate the therapeutic responses of nanomedicines are successfully predicted based on intracellular nanoparticle exposure rather than the overall accumulation in tumour mass. This nonlinear optical nanotechnology offers a valuable imaging tool to evaluate the tumour targeting of new nanomedicines and stratify patients for personalised cancer therapy.

Suggested Citation

  • Qingqing Yin & Anni Pan & Binlong Chen & Zenghui Wang & Mingmei Tang & Yue Yan & Yaoqi Wang & Heming Xia & Wei Chen & Hongliang Du & Meifang Chen & Chuanxun Fu & Yanni Wang & Xia Yuan & Zhihao Lu & Qi, 2021. "Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22678-z
    DOI: 10.1038/s41467-021-22678-z
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    Cited by:

    1. Mingmei Tang & Binlong Chen & Heming Xia & Meijie Pan & Ruiyang Zhao & Jiayi Zhou & Qingqing Yin & Fangjie Wan & Yue Yan & Chuanxun Fu & Lijun Zhong & Qiang Zhang & Yiguang Wang, 2023. "pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Meijie Pan & Ruiyang Zhao & Chuanxun Fu & Mingmei Tang & Jiayi Zhou & Bin Ma & Jianxiong Liu & Ye Yang & Binlong Chen & Qiang Zhang & Yiguang Wang, 2024. "Tuning nanoparticle core composition drives orthogonal fluorescence amplification for enhanced tumour imaging," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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