Abstract
A major impediment to the long-term in vivo vascular imaging is a lack of suitable probes and contrast agents. Our developed mercaptosuccinic acid (MSA) capped cadmium telluride/cadmium sulfide (CdTe/CdS) ultrasmall quantum dots (QDs) have high fluorescent quantum yield, long fluorescence lifetime and long half-life in blood, allowing high resolution long-term intravital vascular imaging. In this study, we showed that these QDs can be used to visualize the in vivo the vasculature in normal and cancerous livers in mice using multiphoton microscopy (MPM) coupled with fluorescence lifetime imaging (FLIM), with cellular resolution (~1 µm) up to 36 h after intravenous injection. Compared to highly regulated and controlled sinusoids in normal liver tissue, disordered, tortuous, and immature neovessels were observed in tumors. The utilized imaging methods have great potential as emerging tools in diagnosis and monitoring of treatment response in cancer.
Highlights
Optical-based intravital imaging of vasculature is an emerging modality for studying vascular structure, function, and angiogenesis
quantum dots (QDs) applied for in vivo imaging of tumor vasculature were firstly reported by Cai et al [6], where the majority of QDs were found in the tumor vasculature with few binding to tumor cells
This study confirmed that QDs did not extravasate but only targeted the vascular integrin αVβ3, which is involved in tumor angiogenesis
Summary
Optical-based intravital imaging of vasculature is an emerging modality for studying vascular structure, function, and angiogenesis. This study confirmed that QDs did not extravasate but only targeted the vascular integrin αVβ3, which is involved in tumor angiogenesis These studies only reported in vivo QDs distribution in tumors at the organ-level or by ex vivo sections. We have successfully synthesized long-circulating QDs in our laboratory and their in vivo fate has been fully investigated [4,5,8] Our results showed these QDs mainly distributed in the liver and kidney. We further investigated the spatiotemporal disposition of QDs in the liver and kidney by multiphoton microscopy (MPM) [4] These QDs were evenly distributed in the blood vessels of these organs and circulated for a long time, but were not taken up by hepatocytes and tubular cells [4]. We further applied these ultrasmall water-dispersible cadmium telluride/cadmium sulfide (CdTe/CdS) QDs for the long-term intravital imaging of vasculature in normal and cancerous livers
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