A near-infrared fluorescent probe with two-photon excitation for in situ imaging of NQO1 in human colorectum cancer tissue

• Published in: Talanta (Oxford) 2024-07, Vol.274, p.126018-126018, Article 126018
• Main Authors: Jiang, Wei, An, Weizhen, Huang, Zhongxi, Xu, Chenfeng, Shen, Qian, Pu, Chibin, Zhang, Shiji, Wu, Qiong, Li, Lin, Yu, Changmin
• Format: Article
• Language: English
• Subjects: absorption; biocompatibility; biomarkers; drug therapy; early diagnosis; fluorescent dyes; free radicals; Human colorectum cancer; humans; In situ imaging; microscopy; NIR emission; NQO1 detection; quinones; Two-photon excitation
• ISSN: 0039-9140; 1873-3573
• DOI: 10.1016/j.talanta.2024.126018

Colorectum cancer has become one of the most fatal cancer diseases, in which NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a role in intracellular free radical reduction and detoxification and has been linked to colorectum cancer and chemotherapy resistance. Therefore, rational design of optical probe for NQO1 detection is urgent for the early diagnosis of colorectum cancer. Herein, we have developed a novel two-photon fluorescent probe, WHFD, which is capable of selectively detecting of intracellular NQO1 with two-photon (TP) absorption (800 nm) and near-infrared emission (620 nm). Combination with a substantial Stokes shift (175 nm) and biocompatibility, we have assessed its suitability for in vivo imaging of endogenous NQO1 activities from HepG2 tumor-bearing live animals with high tissue penetration up to 300 μm. Particularly, we for the first time used the probe to image NQO1 activities from human colorectum cancer samples by using TP microscopy, and proving our probe possesses reliable diagnostic performance to directly in situ imaging of cancer biomarker and can clearly distinguish the boundary between human colorectum cancer tissue and their surrounding normal tissue, which shows great potential for the intraoperative navigation. [Display omitted] •A near-infrared two-photon fluorescent probe for in situ imaging of NQO1 is successfully developed.•This probe shows excellent specificity to NQO1 via computational docking over various interfering biological species.•High tissue penetration for in vivo imaging is achieved due to its Stokes shift, two-photon absorption and NIR emission.•Our probe is firstly used to detecting endogenous NQO1 activities from clinically human colorectum tumor samples.