1200nm NIR-II Novel Yellow Anthracene Dye Application: Highly Effective Tumor Angiography and Photothermal Therapy

Key points of this article: Photothermal therapy (PTT) is a non-invasive treatment that induces apoptosis and necrosis through local hyperthermia and has effective tumor lethality, but the increase in the therapeutic effect of NIR-II PTT relies on non-radiation attenuation, which sacrifices the fluorescence brightness

Protocol 1: Schematic diagram of CL4/FBS construction, balanced use of fluorescence and light heat for tumor angiography and photothermal therapy

After CL4 is complexed with FBS, fluorescence imaging and PTT treatment

Figure 1: a) Molecular structure

Table 1: Photophysical properties of CLs and DFT calculations

First, study the spectral properties

Figure 2: a) Chronological emission spectra

Next, study the properties of

Figure 3: a) Heating curve

Next, the photothermal properties

Figure 4: a) Images

Subsequently, the effect of PTT on CL4/FBS was studied in vitro

Figure 5: a) NIR-II FL

Next, the most basic properties of

Figure 6: a) Systemic NIR-II fluorescence imaging after intravenous CL4/FBS and CL4 injections in 4T1 tumor-bearing mice, and enlarged images

Next, the enrichment of CL4/FBS in tumors was studied
.
As shown in Figure 6a-6b, after intravenous injection of CL4/FBS, the tumor brightness gradually increases, and the tumor brightness is the greatest after 32 h of injection, while after intravenous injection of CL4, NIR-II fluorescence
is almost not observed at the tumor site.
After studying the main organs and tumors of mice, it was found that CL4/FBS was more efficiently enriched in tumors than CL4; In addition, CL4/FBS and CL4 accumulate in both the liver and spleen, suggesting that it is possible that their metabolic pathway in the body is the hepatobiliary system (Figure 6c-d
).
These results suggest that CL4/FBS can be used as an effective NIR-II fluorescent agent for tumor imaging
.

Figure 7: a) Time-resolved infrared thermal imaging
of mice in the laser and PTT groups over time.
b) Changes in tumor temperature in
different groups.
c) Changes in tumor volume in mice over 14 days after different treatments
.
d) Mouse photos on days 0 and 14 after different treatments
.
e) Photo
of the tumor on day 14.
f) Weight
of the tumor on day 14.
g) Mouse body weights
after 14 days of different treatments.
h) H&E, Ki67, TUNEL stained images of tumor sections after different treatments
.

Finally, an in vivo NIR-II PTT study was conducted
.
According to the treatment mode, it is divided into 4 groups: (1) control group; (2) CL4/FBS group; (3) laser group; (4) PTT group
.
As shown in Figure 7a-7b, the tumor temperature in the PTT group increased rapidly, while the tumor temperature in the other groups did not change
significantly.
Next, the volume and weight of the tumors were examined and it was found that tumor growth was significantly inhibited in only the PTT group (Figures 7c-7f
).
This shows that CT4/FBS has good tumor suppressive activity
.
And as shown in Figure 7g, during treatment, the weight change of each group of mice is negligible, indicating that there are no obvious adverse reactions
in each group.
Next, the inhibition mechanism of PTT on tumor growth was further explored, as shown in Figure 7h, the H&E staining image of tumor tissue in the PTT group showed severe apoptosis and necrosis of tumor cells, and the Ki67 and TUNEL immunofluorescence staining images showed mild proliferation and obvious apoptosis signals of tumor cells, and the results confirmed that CL4/FBS PTT had a good inhibitory effect on tumors
.

Summary: The author synthesized four new NIR-II dye CLs
with an emission wavelength of more than 1200 nm.
Among them, CL4 has the strongest fluorescence intensity and the highest PCE
after complexing with FBS.
In NIR-II FL imaging, tumor blood vessels can be clearly visualized and tumor growth can be significantly inhibited, and the balanced use of fluorescent imaging and PTT treatment
has been successfully achieved.

References

doi.
org/10.
1002/smll.
202202078.

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Near-infrared two-zone small animal in vivo fluorescence imaging system - MARS

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Shanghai Hengguang Zhiying Medical Technology Co.
, Ltd.
, focusing on near-infrared two-zone imaging technology
.
Committed to providing advanced, integrated imaging solutions for research in biomedical, preclinical and clinical applications
.
Independently developed the near-infrared two-zone small animal in vivo fluorescence imaging system - MARS
.

Compared with traditional imaging techniques based on visible wavelengths, our technology focuses on X-ray, ultraviolet, infrared, shortwave infrared, terahertz range, which can provide clear imaging effects for researchers in a series of disciplines such as oncology, neurology, cardiovascular, pharmacokinetics, etc.
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