Biomarker-responsive nanoprobe with aggregation-induced emission for locating and guiding resection of deep-seated tumors via optoacoustic and NIR fluorescence imaging

Abstract

Surgical resection of tumors often is a necessary part of a curative regimen for several types of cancer, and successful tumor resection depends on accurately locating the tumor and precisely differentiating between tumor tissue and normal tissue, as this affects not only survival but also life quality for patients. Herein, the biomarker-responsive nanoprobe DHXI@HSA has been fabricated for accurate location of deep-seated tumors and imaging-guided tumor resection surgery. The nanoprobe was obtained via the self-assembly of the probe compound DHXI and recombinant human serum albumin (HSA); with HSA as the integral component, the nanoprobe has good biocompatibility and sufficient water dispersibility for applications in biological milieu. The nanoprobe is specifically responsive towards the biomarker NAD(P)H quinone oxidoreductase isozyme 1 (NQO1) that is overexpressed in cancerous tumors; upon reaction with the enzyme NQO1, the strong electron-deficient group quinone propionate in the probe compound transforms into the electron-rich hydroxyl group, and thereby the probe is activated; correspondingly with aggregation induced emission (AIE), the activated nanoprobe produces evident near-infrared (NIR) fluorescence and salient optoacoustic signal for fluorescence imaging and multispectral optoacoustic tomography (MSOT) imaging. With the in situ response to NQO1 in the tumors, the nanoprobe can locate some deep-seated tumors including liver tumors with 3D information in mouse models via MSOT imaging, and offer intraoperative guidance for tumor resection by distinguishing between normal and tumor tissues via NIR fluorescence imaging.