Tuning nanoparticle core composition drives orthogonal fluorescence amplification for enhanced tumour imaging

Meijie Pan, Ruiyang Zhao, Chuanxun Fu, Mingmei Tang, Jiayi Zhou, Bin Ma, Jianxiong Liu, Ye Yang, Binlong Chen, Qiang Zhang and Yiguang Wang ()
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Meijie Pan: Peking University
Ruiyang Zhao: Peking University
Chuanxun Fu: Peking University
Mingmei Tang: Peking University
Jiayi Zhou: Peking University
Bin Ma: Peking University
Jianxiong Liu: Peking University
Ye Yang: Peking University
Binlong Chen: Peking University
Qiang Zhang: Peking University
Yiguang Wang: Peking University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Tumour detection with high selectivity and sensitivity is crucial for delineating tumour margins and identifying metastatic foci during image-guided surgery. Optical nanoprobes with preferential tumour accumulation is often limited by inefficient amplification of biological signals. Here, we report the design of a library of hydrophobic core-tunable ultra-pH-sensitive nanoprobes (HUNPs) for orthogonally amplifying tumour microenvironmental signals on multiple tumour models. We find that tuning the hydrophobicity of nanoparticle core composition with non-ionizable monomers can enhance cellular association of HUNPs by more than ten-fold, resulting in a high cellular internalization efficiency of HUNPs with up to 50% in tumours. Combining high tumour accumulation and high cell internalization efficiency, HUNPs show orthogonally amplified fluorescence signals, permitting the precise locating and delineating margins between malignant lesions and normal tissues with high contrast-to-noise ratio and resolution. Our study provides key strategies to design nanomedicines with high intracellular bioavailability for cancer detection, drug/gene delivery, and therapy.

Date: 2024
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DOI: 10.1038/s41467-024-52029-7

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