Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy

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, Qiang Zhang and Yiguang Wang ()
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Qingqing Yin: 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
Yiguang Wang: Peking University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-22678-z

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