Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging

Yue Yan, Binlong Chen, Qingqing Yin, Zenghui Wang, Ye Yang, Fangjie Wan, Yaoqi Wang, Mingmei Tang, Heming Xia, Meifang Chen, Jianxiong Liu, Siling Wang, Qiang Zhang and Yiguang Wang ()
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Yue Yan: Peking University
Binlong Chen: Peking University
Qingqing Yin: Peking University
Zenghui Wang: Peking University
Ye Yang: Peking University
Fangjie Wan: Peking University
Yaoqi Wang: Peking University
Mingmei Tang: Peking University
Heming Xia: Peking University
Meifang Chen: Peking University
Jianxiong Liu: Peking University
Siling Wang: Shenyang Pharmaceutical University
Qiang Zhang: Peking University
Yiguang Wang: Peking University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Efficient delivery of payload to intracellular targets has been identified as the central principle for nanomedicine development, while the extracellular targets are equally important for cancer treatment. Notably, the contribution of extracellularly distributed nanoparticles to therapeutic outcome is far from being understood. Herein, we develop a pH/light dual-responsive monochromatic ratiometric imaging nanoparticle (MRIN), which functions through sequentially lighting up the intracellular and extracellular fluorescence signals by acidic endocytic pH and near-infrared light. Enabled by MRIN nanotechnology, we accurately quantify the extracellular and intracellular distribution of nanoparticles in several tumor models, which account for 65–80% and 20–35% of total tumor exposure, respectively. Given that the majority of nanoparticles are trapped in extracellular regions, we successfully dissect the contribution of extracellularly distributed nanophotosensitizer to therapeutic efficacy, thereby maximize the treatment outcome. Our study provides key strategies to precisely quantify nanocarrier microdistribtion and engineer multifunctional nanomedicines for efficient theranostics.

Date: 2022
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DOI: 10.1038/s41467-022-29679-6

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