Xu Limei, Xiong Weiwei, Zhang Shiling, Pan Jiajia, Liu Yingqi, Liu Qiulin, Wu Haojie, Li Lingling, Zhu Jun-Jie, Zheng Fenfen
School of Environmental & Chemical Engineering, Jiangsu University of Science and Technology, Changhui Rd. 666, Zhenjiang, Jiangsu 212003, China.
Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
Anal Chem. 2025 Feb 4;97(4):2463-2471. doi: 10.1021/acs.analchem.4c06166. Epub 2025 Jan 26.
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@mSiO 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.
肿瘤的早期诊断可通过局部治疗干预对原发性癌症进行有效治疗。然而，开发用于灵敏、简便且早期肿瘤（尤其是直径小于2毫米的肿瘤）检测的诊断工具仍然是一项挑战。在此，我们展示了一种生物标志物可激活的纳米探针，其能够实现近红外（NIR）光热放大信号，用于肿瘤的荧光成像和尿液分析。这种可激活的纳米探针是通过将可经肾脏清除的近红外ZW800染料封装到带有透明质酸的CuS@mSiO核壳纳米颗粒中构建而成。纳米探针可在肿瘤部位积聚，并对肿瘤相关的透明质酸酶产生响应，进行原位酶催化去封装，以释放可经肾脏清除的ZW800染料，用于活体小鼠肿瘤的荧光成像和尿液分析。值得注意的是，借助近红外激光照射，CuS核的光热效应通过光热增强的ZW800释放促进了用于肿瘤诊断的信号放大，提供了高特异性和灵敏度。由于生物标志物的特异性以及时空可控的近红外照射，纳米探针能够选择性地激活其近红外荧光（NIRF）信号，以可视化活体小鼠体内的肿瘤，并便于将纳米探针转化为用于体外诊断肿瘤进展的人工尿液生物标志物探针。在4T1荷瘤小鼠模型中，可激活的纳米探针能够实现对肿瘤（直径1.9毫米）的超灵敏检测。本研究提供了一种通过近红外荧光成像或简单尿液检测进行早期肿瘤诊断的非侵入性且光热信号放大的方法。
