Acid and Hypoxia Tandem-Activatable Deep Near-Infrared Nanoprobe for Two-Step Signal Amplification And Early Detection of Cancer.

The early detection of cancers can significantly change outcomes even with existing treatments. However, ∼50% of cancers still cannot be detected until they reach an advanced stage, highlighting the great challenges in the early detection. Here, w e report on an ultrasensitive deep near-infrared (NIR) nanoprobe that is successively responsive to tumor acidity and hypoxia. W e demonstrate that the new nanoprobe specifically detects tumor hypoxia microenvironment based on deep NIR imaging in ten different types of tumor models using cancer cell lines and patient-tissue derived xenograft tumors. By combining the acidity and hypoxia specific two-step signal amplification with a deep NIR detection, the reported nanoprobe enables the ultrasensitive visualization of hundreds of tumor cells or small tumors with a size of 260 μm in whole-body imaging or 115 μm metastatic lesions in lung imaging. As a result, it reveals that tumor hypoxia can occur as early as the lesions contain only several hundred cancer cells. This article is protected by copyright. All rights reserved.