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A new H₂S-specific near-infrared fluorescence-enhanced probe that can visualize the H₂S level in colorectal cancer cells in mice.

ABSTRACT: Near-infrared (NIR) fluorescence-based sensors capable of selective detection of H₂S in vivo would be useful tools to understand the mechanisms of diseases. A new NIR fluorescence probe 1 was developed for the detection of endogenous H₂S in colorectal cancer cells in mice. 1 displayed an 87-fold fluorescence enhancement at 796 nm (with excitation at 730 nm) when reacted with H₂S in a buffer (pH 7.4). 1 was water-soluble, cell-membrane-permeable, had low cytotoxicity and high selectivity and sensitivity for H₂S. The properties of 1 enable its use in monitoring endogenous H₂S in living cells, tissues, and mice. The bioimaging results indicated that (1) d-Cys could induce endogenous H₂S production in living cells and stimulate angiogenesis; (2) tail intravenous injection of 1 into mice generated strong fluorescence in the liver while intraperitoneal injection of d-Cys could further enhance fluorescence in the liver in vivo; (3) importantly, endogenous H₂S in colorectal cancer cells (HCT116, HT29) in vitro and in murine tumor models could be quickly and selectively detected by intratumoral injection of 1. These results indicated that our new probe could serve as an efficient tool for the detection of cellular H₂S in living animals and even for cancer diagnosis.

SUBMITTER: Zhang K

PROVIDER: S-EPMC5426460 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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A new H2S-specific near-infrared fluorescence-enhanced probe that can visualize the H2S level in colorectal cancer cells in mice.

Zhang Kun K Zhang Jie J Xi Zhen Z Li Lu-Yuan LY Gu Xiangxiang X Zhang Qiang-Zhe QZ Yi Long L

Chemical science 20170117 4

Near-infrared (NIR) fluorescence-based sensors capable of selective detection of H2S in vivo would be useful tools to understand the mechanisms of diseases. A new NIR fluorescence probe 1 was developed for the detection of endogenous H2S in colorectal cancer cells in mice. 1 displayed an 87-fold fluorescence enhancement at 796 nm (with excitation at 730 nm) when reacted with H2S in a buffer (pH 7.4). 1 was water-soluble, cell-membrane- ...[more]

PMID: 28553513

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Project description:BACKGROUND:To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. METHODS:The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96?h postinjection, and the biodistribution assays were performed using NIRF imaging. RESULTS:In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. CONCLUSIONS:COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

Dataset Information

A new H₂S-specific near-infrared fluorescence-enhanced probe that can visualize the H₂S level in colorectal cancer cells in mice.

Publications

A new H<sub>2</sub>S-specific near-infrared fluorescence-enhanced probe that can visualize the H<sub>2</sub>S level in colorectal cancer cells in mice.

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