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. 2018 Nov 20;10(4):244.
doi: 10.3390/pharmaceutics10040244.

Anionic Long-Circulating Quantum Dots for Long-Term Intravital Vascular Imaging

Haolu Wang  1 , Haotian Yang  2 , Zhi Ping Xu  3 , Xin Liu  4 , Michael S Roberts  5   6 , Xiaowen Liang  7
Affiliations

Anionic Long-Circulating Quantum Dots for Long-Term Intravital Vascular Imaging

Haolu Wang et al. Pharmaceutics. .

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.

Keywords: blood vessels; intravital imaging; quantum dots.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Plasma concentration of QDs following an intravenous injection detected by ICP-MS and it was fitted by a two-compartment model. Symbols represent the mean experimental data and error bars represent standard deviation. The solid lines are simulated by a two-compartment model.
Figure 2
Figure 2
Fluorescence intensity image of mouse blood after QDs administration recorded at λExc/λEm: 900/515 to 620 nm (A); Fluorescence lifetime properties of mouse blood after QDs administration measured by MPM-FLIM (B). Pseudocolored fluorescence lifetime image (τm: 0–10,000 ps; blue-green-red) recorded at λExc/λEm: 900/515 to 620 nm (scale bar: 160 μm).
Figure 3
Figure 3
Multiphoton microscopy coupled with fluorescence lifetime imaging (MPM-FLIM) images of normal liver tissue and hepatocellular carcinoma after QDs injection. Narrow arrow indicates disordered and tortuous vasculature of hepatocellular carcinoma with inefficient blood perfusion and filled arrow indicates larger vessels connected to the tumor vasculature. (A,E) Fluorescence intensity image recorded at λExc/λEm: 740/350 to 450 nm; (B,F) Fluorescence intensity image recorded at λExc/λEm: 900/515 to 620 nm; (C,G) Pseudocolored fluorescence lifetime image (τm: 0–2500 ps; blue-green-red) recorded at λExc/λEm: 740/350 to 450 nm or (D,H) recorded at λExc/λEm: 900/515 to 620 nm. (Scale bar: 40 μm).
Figure 4
Figure 4
Time profile of QDs intensity in vasculature of normal liver after bolus injection. (A) Real-time hepatic disposition of QDs, (Scale bar: 160 μm); (B) Time profile of QDs intensity per pixel. The symbols represent measured data and the line represents the connecting curve. Error bar represents the standard deviation (n = 3).
Figure 5
Figure 5
Representative organ histology images of control and QDs treated mice. QDs treated organs were collected 7 days or 30 days after intravenous injection of QDs. (Scale bar: 40 μm).
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