Hypoxia plays a crucial role in cancer progression, and it has great significance for monitoring hypoxic level in biosystems. Cancer stem cells (CSCs) represent a small population of tumour cells that regard as the key to seed tumours. The survival of CSCs depend on the tumour microenvironment, which is distinct region has the hypoxic property. Therefore, the detection of the hypoxic CSC niche plays a pivotal role in the destructing the 'soil' of CSCs, and eliminating CSCs population. Numerous one-photon excited fluorescent probes have been developed to indicate the hypoxic status in tumours through the detection of nitroreductase (NTR) level. However, the biomedical application of one-photon fluorescent probes is limited due to the poor tissue penetration. In the present work, we reported a two-photon fluorescent probe to detect the NTR in CSCs and monitor the hypoxic microenvironment in vivo. The two-photon fluorescent molecular probe with a hypoxic specific response group can be reduced by NTR under hypoxic conditions. We used the two-photon probe to detect the hypoxia status of 3D cultured-CSCs in vitro and in vivo CSCs' microenvironment in tumour. The two-photon absorption cross section extends fluorescent excitation spectra to the near infrared region, which dramatically promotes the tissue penetration for hypoxic microenvironment detection of CSC in vivo.

中文翻译：

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用于检测癌干细胞硝基还原酶和缺氧特异性微环境的双光子荧光探针

缺氧在癌症进展中起着至关重要的作用，对于监测生物系统中的缺氧水平具有重要意义。癌症干细胞 (CSC) 代表一小群肿瘤细胞，被视为种子肿瘤的关键。CSCs 的存活取决于肿瘤微环境，这是不同区域具有缺氧特性。因此，缺氧CSC生态位的检测在破坏CSCs的“土壤”和消除CSCs种群中起着举足轻重的作用。已经开发了许多单光子激发的荧光探针，通过检测硝基还原酶 (NTR) 水平来指示肿瘤中的缺氧状态。然而，由于组织穿透性差，单光子荧光探针的生物医学应用受到限制。在目前的工作中，我们报道了一种双光子荧光探针来检测 CSC 中的 NTR 并监测体内缺氧微环境。具有缺氧特异性反应基团的双光子荧光分子探针在缺氧条件下可被NTR还原。我们使用双光子探针检测 3D 培养的 CSCs 在体外和体内 CSCs 在肿瘤中的微环境的缺氧状态。双光子吸收截面将荧光激发光谱扩展到近红外区域，极大地促进了体内 CSC 缺氧微环境检测的组织渗透。我们使用双光子探针检测 3D 培养的 CSCs 在体外和体内 CSCs 在肿瘤中的微环境的缺氧状态。双光子吸收截面将荧光激发光谱扩展到近红外区域，极大地促进了体内 CSC 缺氧微环境检测的组织渗透。我们使用双光子探针检测 3D 培养的 CSCs 在体外和体内 CSCs 在肿瘤中的微环境的缺氧状态。双光子吸收截面将荧光激发光谱扩展到近红外区域，极大地促进了体内 CSC 缺氧微环境检测的组织渗透。