Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China; College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding, 071002, China.
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China; College of Chemistry and Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding, 071002, China.
Anal Chim Acta. 2018 Sep 18;1024:177-186. doi: 10.1016/j.aca.2018.03.030. Epub 2018 Mar 29.
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.
缺氧在癌症进展中起着至关重要的作用，因此监测生物系统中的缺氧水平具有重要意义。癌症干细胞 (CSC) 是一小部分肿瘤细胞，被认为是肿瘤形成的关键。CSC 的存活依赖于肿瘤微环境，肿瘤微环境是具有缺氧特性的独特区域。因此，检测缺氧的 CSC 生态位在破坏 CSC 的“土壤”和消除 CSC 群体方面起着关键作用。已经开发了许多单光子激发荧光探针，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。在本工作中，我们报道了一种用于检测 CSCs 中 NTR 和监测体内缺氧微环境的双光子荧光探针。具有缺氧特异性反应基团的双光子荧光分子探针可在缺氧条件下被 NTR 还原。我们使用双光子探针在体外和体内肿瘤中检测 3D 培养的 CSCs 的缺氧状态和 CSCs 微环境。双光子吸收截面将荧光激发光谱扩展到近红外区域，这极大地促进了体内 CSC 缺氧微环境检测的组织穿透性。
