A K+-sensitive AND-gate dual-mode probe for simultaneous tumor imaging and malignancy identification

Qiyue Wang; Fangyuan Li; Zeyu Liang; Hongwei Liao; Bo Zhang; Peihua Lin; Xun Liu; Shen Hu; Jiyoung Lee; Daishun Ling

doi:10.1093/nsr/nwac080

A K⁺-sensitive AND-gate dual-mode probe for simultaneous tumor imaging and malignancy identification

Natl Sci Rev. 2022 Apr 28;9(7):nwac080. doi: 10.1093/nsr/nwac080. eCollection 2022 Jul.

Authors

Qiyue Wang¹, Fangyuan Li¹, Zeyu Liang¹, Hongwei Liao¹, Bo Zhang², Peihua Lin¹, Xun Liu², Shen Hu³, Jiyoung Lee¹, Daishun Ling¹

Affiliations

¹ Institute of Pharmaceutics, Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
² Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
³ Department of Obstetrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China.

Abstract

Although molecular imaging probes have the potential to non-invasively diagnose a tumor, imaging probes that can detect a tumor and simultaneously identify tumor malignancy remain elusive. Here, we demonstrate a potassium ion (K⁺) sensitive dual-mode nanoprobe (KDMN) for non-invasive tumor imaging and malignancy identification, which operates via a cascaded 'AND' logic gate controlled by inputs of magnetic resonance imaging (MRI) and fluorescence imaging (FI) signals. We encapsulate commercial K⁺ indicators into the hollow cavities of magnetic mesoporous silica nanoparticles, which are subsequently coated with a K⁺-selective membrane that exclusively permits the passage of K⁺ while excluding other cations. The KDMN can readily accumulate in tumors and enhance the MRI contrast after systemic administration. Spatial information of the tumor lesion is thus accessible via MRI and forms the first layer of the 'AND' gate. Meanwhile, the KDMN selectively captures K⁺ and prevents interference from other cations, triggering a K⁺-activated FI signal as the second layer of the 'AND' gate in the case of a malignant tumor with a high extracellular K⁺ level. This dual-mode imaging approach effectively eliminates false positive or negative diagnostic results and allows for non-invasive imaging of tumor malignancy with high sensitivity and accuracy.

Keywords: MRI; dual-mode imaging probe; fluorescence imaging; potassium ion; tumor malignancy identification.