Two-photon fluorescent probe for detection of nitroreductase and hypoxia-specific microenvironment of cancer stem cell

• Published in: Analytica chimica acta 2018-09, Vol.1024, p.177-186
• Main Authors: Liu, Yajing, Liu, Wei, Li, Hongjuan, Yan, Weixiao, Yang, Xinjian, Liu, Dandan, Wang, Shuxiang, Zhang, Jinchao
• Format: Article
• Language: English
• Subjects: Absorption cross sections; Atoms & subatomic particles; Biomedical materials; Cancer; Cancer stem cell; Excitation spectra; Fluorescence; Fluorescent indicators; Hypoxia; Infrared spectra; Microenvironment; Near infrared radiation; Nitroreductase; Penetration; Photon absorption; Probes; Proteins; Stem cells; Tumor microenvironment; Tumors; Two-photon
• ISSN: 0003-2670; 1873-4324
• DOI: 10.1016/j.aca.2018.03.030

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. The NTR-dependent two-photon probe has potential to detect the CSCs in hypoxic niche due to the overexpression of HIFs, which enhanced the NTR activity in CSCs. The two-photon fluorescent molecular probe with a hypoxic specific response group, which can be reduced by nitroreductase (NTR) under hypoxic conditions and then undergo intra molecular charge transfer and intra molecular lipid exchange to release 2-carboxy-2′-hydroxybiphenyl (BCM), which emits strong fluorescent. The large two-photon absorption cross section extends fluorescent excitation spectra to the NIR region, allowing light penetration for deep-tissue imaging, which will greatly promote the tissue penetration and application in biological systems. [Display omitted] •A two-photon fluorescence probe is developed.•The two-photon fluorescence probe detected the hypoxic microenvironment of cancer stem cells (CSCs) in vivo.•The two-photon absorption cross section extends fluorescent excitation spectra to the NIR region, allowing light penetration for deep-tissue imaging, which will greatly promote the application in biological systems.