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- Title
Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy.
- Authors
Yin, Qingqing; Pan, Anni; Chen, Binlong; Wang, Zenghui; Tang, Mingmei; Yan, Yue; Wang, Yaoqi; Xia, Heming; Chen, Wei; Du, Hongliang; Chen, Meifang; Fu, Chuanxun; Wang, Yanni; Yuan, Xia; Lu, Zhihao; Zhang, Qiang; Wang, Yiguang
- 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. Quantification of intratumoral nanoparticles internalisation in vivo is crucial but challenging. Here, the authors develop a binary ratiometric nanoreporter that can quantify internalisation and predict nanotherapeutic responses based on intracellular nanoparticle exposure.
- Subjects
NANOMEDICINE; GENE targeting; FORECASTING; CANCER treatment; TITANIUM dioxide nanoparticles; NANOCARRIERS
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22678-z