Near-Infrared pH-Activatable Fluorescent Probes for Imaging Primary and Metastatic Breast Tumors

详细信息    查看全文

• 作者：Hyeran Lee ; Walter Akers ; Kumar Bhushan ; Sharon Bloch ; Gail Sudlow ; Rui Tang ; Samuel Achilefu
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：April 20, 2011
• 年：2011
• 卷：22
• 期：4
• 页码：777-784
• 全文大小：953K
• 年卷期：v.22,no.4(April 20, 2011)
• ISSN：1520-4812

文摘

Highly tumor selective near-infrared (NIR) pH-activatable probe was developed by conjugating pH-sensitive cyanine dye to a cyclic arginine-glycine-aspartic acid (cRGD) peptide targeting 伪_v尾₃ integrin (ABIR), a protein that is highly overexpressed in endothelial cells during tumor angiogenesis. The NIR pH-sensitive dye used to construct the probe exhibits high spectral sensitivity with pH changes. It has negligible fluorescence above pH 6 but becomes highly fluorescent below pH 5, with a pK_a of 4.7. This probe is ideal for imaging acidic cell organelles such as tumor lysosomes or late endosomes. Cell microscopy data demonstrate that binding of the cRGD probe to ABIR facilitated the endocytosis-mediated lysosomal accumulation and subsequent fluorescence enhancement of the NIR pH-activatable dye in tumor cells (MDA-MB-435 and 4T1/luc). A similar fluorescence enhancement mechanism was observed in vivo, where the tumors were evident within 4 h post injection. Moreover, lung metastases were also visualized in an orthotopic tumor mouse model using this probe, which was further confirmed by histologic analysis. These results demonstrate the potential of using the new integrin-targeted pH-sensitive probe for the detection of primary and metastatic cancer.