Deng Min, Wang Peipei, Zhai Zibo, Liu Ying, Cheng Dan, He Longwei, Li Songjiao
Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang 421002, China.
Department of Gastroenterology, Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, PR China.
Anal Chem. 2025 Feb 11;97(5):2998-3008. doi: 10.1021/acs.analchem.4c06015. Epub 2025 Jan 31.
Revealing changes in the tumor microenvironment is crucial for understanding cancer and developing sensitive methods for precise cancer imaging and diagnosis. Intracellular hydrogen peroxide (HO) and microenvironmental factors (e.g., viscosity and polarity) are closely linked to various physiological and pathological processes, making them potential biomarkers for cancer. However, a triple-response theranostic probe for precise tumor imaging and therapy has not yet been achieved due to the lack of effective tools. Herein, we present a mitochondria-targeting near-infrared (NIR) fluorescent probe, , capable of simultaneously monitoring HO, viscosity, and polarity through dual NIR channels. The probe specifically detects HO via NIR emission (λ = 650 nm) and shows high sensitivity to microenvironmental viscosity/polarity in the deep NIR channel (λ ≈ 750 nm). Furthermore, the probe not only monitors mitochondrial polarity, viscosity, and fluctuations in endogenous/exogenous HO levels but also distinguishes cancer cells from normal cells through multiple parameters. Additionally, VPH-5DF can be employed to monitor alterations in HO levels, as well as changes in viscosity and polarity, during drug-induced pyroptosis in living cells. After treatment with VPH-5DF, chemotherapy-induced oxidative damage to the mitochondria in tumor cells activated the pyroptosis pathway, leading to a robust antitumor response, as evidenced in xenograft tumor models. Thus, this triple-response theranostic prodrug offers a new platform for precise cancer diagnosis and anticancer chemotherapy.
揭示肿瘤微环境的变化对于理解癌症以及开发用于精确癌症成像和诊断的灵敏方法至关重要。细胞内过氧化氢（HO）和微环境因素（如粘度和极性）与各种生理和病理过程密切相关，使其成为癌症的潜在生物标志物。然而，由于缺乏有效的工具，尚未实现用于精确肿瘤成像和治疗的三响应诊疗探针。在此，我们提出了一种线粒体靶向近红外（NIR）荧光探针，能够通过双近红外通道同时监测HO、粘度和极性。该探针通过近红外发射（λ = 650 nm）特异性检测HO，并在深近红外通道（λ ≈ 750 nm）中对微环境粘度/极性表现出高灵敏度。此外，该探针不仅监测线粒体极性、粘度以及内源性/外源性HO水平的波动，还通过多个参数区分癌细胞和正常细胞。此外，VPH-5DF可用于监测活细胞药物诱导的焦亡过程中HO水平的变化以及粘度和极性的变化。用VPH-5DF处理后，化疗诱导的肿瘤细胞线粒体氧化损伤激活了焦亡途径，导致强大的抗肿瘤反应，异种移植肿瘤模型证明了这一点。因此，这种三响应诊疗前药为精确癌症诊断和抗癌化疗提供了一个新平台。
