Near-Infrared Photothermally Assisted Nanoprobes Boost Signal Amplification for Fluorescence Imaging and Urinalysis of Tumor

Early diagnosis of tumors allows effective treatment of primary cancers through localized therapeutic interventions. However, developing diagnostic tools for sensitive, simple, and early tumor (especially less than 2 mm in diameter) detection remains a challenge. Herein, we presented a biomarker-activatable nanoprobe that enabled a near-infrared (NIR) photothermally amplified signal for fluorescence imaging and urinalysis of tumor. This activatable nanoprobe was constructed by encapsulating renal-clearable NIR ZW800 dyes into a CuS@mSiO₂ core-shell nanoparticle with hyaluronic acid. The nanoprobes could accumulate at the tumor site and respond to tumor-associated hyaluronidase, undergoing in situ enzyme-catalyzed decapsulation to release renal-clearable ZW800 dyes for fluorescence imaging and uranalysis of tumor in living mice. Notedly, with the aid of NIR laser irradiation, the photothermal effect of CuS core boosted signal amplification for tumor diagnosis via photothermally enhanced ZW800 release, providing high specificity and sensitivity. On account of the biomarker specificity and the spatiotemporally controlled NIR irradiation, the nanoprobes could selectively activate their NIR fluorescence (NIRF) signal to visualize tumors in living mice and allow for the easy translation of the nanoprobe as artificial urinary biomarker probes for in vitro diagnosis of tumor progression. In 4T1 tumor-bearing mice models, the activatable nanoprobes enabled ultrasensitive detection of tumors (1.9 mm in diameter). This study offers a noninvasive and photothermally signal-amplified approach for early tumor diagnosis via NIRF imaging or simple urine tests.