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

Abstract

Although molecular imaging probes have the potential to non-invasively diagnose tumor, imaging probes that can detect 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 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.

Recent progress in the development of small-molecule double-locked logic gate fluorescence probes

“…Actually, bioactive molecules in vivo continue diffusing in blood and tissues, which causes several ''singlesignal'' fluorescence probes to be prematurely and nonspecifically activated during transit, resulting in false-positive or false-negative signals. 20 Furthermore, the synergistic effect of multiple molecules is fundamental in universal physiological activities in organisms, 21 but ''single-signal'' fluorescence probes can sense only one substance of interest, which means that the synergistic effect of two interlinked biomarkers in disease sites cannot be revealed. Although the combined application of multiple ''single-signal'' fluorescence probes can be used to detect multiple biomolecules simultaneously to some extent, the results may be inaccurate because each probe possesses a different diffusion velocity and metabolic rate.…”

“…Following that, Zhang and colleagues synthesized an oxidative stress-triggered fluorescence probe, QM-RSH (20), for monitoring mitochondrial H 2 S levels. 46 In the presence of H 2 O 2 , QM-RSH demonstrated high selectivity and good sensitivity to H 2 S. Furthermore, QM-RSH had be successfully applied to monitor the fluctuation of H 2 S levels under oxidative stress in living cells and zebrafish, which avoiding interference from other physiological processes.…”

Inorganic ion-sensitive imaging probes for biomedical applications

“…The KDMN exhibited highly sensitive K + fluorescence imaging properties and high-performance T 2 MRI capability. 104 Regardless of i.v. or intratumoral injection of KDMNs, a significant discrepancy of fluorescence signals between benign and malignant tumours was observed (Fig.…”

Redox Imbalance Triggered Intratumoral Cascade Reaction for Tumor “turn on” Imaging and Synergistic Therapy

“…[41][42][43] The combination of MRI and FI can exert the advantages of the two imaging techniques, simultaneously achieving high spatial resolution and sensitivity in tumor diagnosis. [44][45][46][47] Based on the above cognition, herein, a multifunctional integrated nanosphere has been designed to diagnose by TME-responsive "turn-on" fluorescence and magnetic resonance imaging in vivo. Meanwhile, the nanospheres have used to eliminate tumors with superior synergistic therapeutic efficiency of intratumoral CDT and chemotherapy by triggering an intratumoral cascade (Scheme 1).…”

“…[ 41–43 ] The combination of MRI and FI can exert the advantages of the two imaging techniques, simultaneously achieving high spatial resolution and sensitivity in tumor diagnosis. [ 44–47 ]…”