Phosphorescence monitoring of hypoxic microenvironment in solid-tumors to evaluate chemotherapeutic effects using the hypoxia-sensitive iridium (III) coordination compound

Zeng, Y and Liu, Y and Shang, J and Ma, J and Wang, R and Deng, L and Guo, Y and Zhong, F and Bai, M and Zhang, S and Wu, D (2015) Phosphorescence monitoring of hypoxic microenvironment in solid-tumors to evaluate chemotherapeutic effects using the hypoxia-sensitive iridium (III) coordination compound. PLoS ONE, 10 (3).

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Abstract

Objectives: To utilize phosphorescence to monitor hypoxic microenvironment in solid-tumors and investigate cancer chemotherapeutic effects in vivo. Methods: A hypoxia-sensitive probe named BTP was used to monitor hypoxic microenvironment in solid-tumors. The low-dose metronomic treatment with cisplatin was used in anti-angiogenetic chemotherapeutic programs. The phosphorescence properties of BTP were detected by a spectrofluorometer. BTP cytotoxicity utilized cell necrosis and apoptosis, which were evaluated by trypan blue dye exclusion and Hoechst33342 plus propidium iodide assays. Tumor-bearing mouse models of colon adenocarcinoma were used for tumor imaging in vivo. Monitoring of the hypoxic microenvironment in tumors was performed with a Maestro 2 fluorescence imaging system. Tumor tissues in each group were harvested regularly and treated with pathological hematoxylin and eosin and immunohistochemical staining to confirm imaging results. Results: BTP did not feature obvious cytotoxicity for cells, and tumor growth in low-dose metronomic cisplatin treated mice was significantly inhibited by chemotherapy. Hypoxic levels significantly increased due to cisplatin, as proven by the expression level of related proteins. Phosphorescence intensity in the tumors of mice in the cisplatin group was stronger and showed higher contrast than that in tumors of saline treated mice. Conclusions: We develop a useful phosphorescence method to evaluate the chemotherapeutic effects of cisplatin. The proposed method shows potential as a phosphorescence imaging approach for evaluating chemotherapeutic effects in vivo , especially anti-angiogenesis.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Zeng, Y Liu, Y Shang, J Ma, J Wang, R Deng, L Guo, Y Zhong, F Bai, M mib63@pitt.edu MIB63 Zhang, S Wu, D
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Takakura, Nobuyuki UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	18 March 2015
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	10
Number:	3
DOI or Unique Handle:	10.1371/journal.pone.0121293
Schools and Programs:	School of Medicine > Radiology
Refereed:	Yes
PubMed ID:	25786221
Date Deposited:	12 May 2015 19:56
Last Modified:	30 Mar 2021 13:56
URI:	http://d-scholarship.pitt.edu/id/eprint/24157

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