​Sci Adv | Zhao Shulin/Zhang Liangliang's research team establishes new methods for photoacoustic imaging and photothermal treatment of tumor growth

Responsible Editor | Enzymic Photoacoustic Imaging is a new biomedical imaging technology based on the combination of light excitation and ultrasound detection.

Since the attenuation of sound waves in biological tissues is 2 to 3 orders of magnitude lower than that of light waves, photoacoustic imaging of biological tissues provides good contrast, super-spatial resolution, high penetration and high sensitivity.

Photoacoustic imaging can avoid strong light scattering in biological tissues and provide a photoacoustic signal that can penetrate 7 cm, with a spatial resolution of up to 100 μm, which exceeds the optical diffusion threshold and penetration depth of traditional optical imaging.

Therefore, photoacoustic imaging is a promising bioimaging technology for deep tissues in the body, which has great application potential in biomedical research and molecular diagnosis of diseases.

Since photoacoustic imaging technology has deeper tissue penetration and higher spatial resolution than traditional optical imaging, it has attracted widespread attention in recent years.

However, to date, there have been few researches on the development of activatable photoacoustic probes.

Considering the advantages of activatable photoacoustic probes, such as high signal-to-noise ratio, real-time detection capability, and the ability to monitor pathological processes in deep tissues at the molecular level, the development of activatable photoacoustic probes is important for promoting biomedical research significance.

On March 19, 2021, the Zhao Shulin/Zhang Liangliang research team of Guangxi Normal University University published an online research paper entitled A tumor microenvironment–induced absorption red-shifted polymer nanoparticle for simultaneously activated photoacoustic imaging and photothermal therapy in Science Advances.

This article proposes a new method of photoacoustic imaging and photothermal therapy for dynamic observation of tumor growth in situ activated by the tumor microenvironment.

Tumor microenvironment response diagnosis and treatment In the diagnosis and treatment of cancer, it can greatly reduce the damage to healthy cells in the process of killing cancer cells, and realize precise medical treatment.

Glutathione (GSH) levels are nearly 1000 times higher in tumor tissues than in normal tissues.

Therefore, GSH can be used as an effective endogenous molecule for cancer diagnosis and tumor microenvironment activation therapy.

In this study, the authors prepared a kind of iron-copper co-doped polyaniline nanoparticles (Fe-Cu@PANI) with a tumor microenvironment-induced red shift of the absorption spectrum.

It was found that the Cu(II) in the nanoparticles can undergo redox reactions with endogenous GSH in tumor tissues.
The redox reactions lead to the etching of the nanoparticles, and as the concentration of GSH increases, the particle size of the nanoparticles gradually decreases.
Small, induces the absorption spectrum of the nanoparticles to red shift from the visible light region to the near-infrared light region, and at the same time activates the tumor's photoacoustic imaging and photothermal therapy (PTT), thereby improving the accuracy of tumor imaging in vivo and the targeting of photothermal therapy Sex.

It shows that the nanoparticles prepared in this study have broad application prospects in the diagnosis and treatment of cancer.

Figure 1.
The preparation principle of Fe-Cu@PANI nanoparticles and the schematic diagram of tumor photoacoustic imaging and PTT activation mechanism.

Based on the principle of photoacoustic imaging proposed in this study, the author used Fe-Cu@PANI nanoparticles as photoacoustic probes to track the growth of tumors during development using photoacoustic imaging.

After 4T1 cells were injected into the roots of the hind legs of the mice, the tumor growth process was monitored on 4, 6, 8, 10, 12, and 14 days.

The monitoring results showed that the photoacoustic signal of tumor tissue gradually increased with the increase of tumor growth time.

In the first 6 days, the photoacoustic signal was relatively low, but from the 6th day to the 12th day, the photoacoustic signal increased significantly with time, and the intensity of the photoacoustic signal stabilized after 12 days.

These results indicate that in tumor tissues of tumor-bearing mice, GSH levels are related to the rate of tumor growth, and the prepared Fe-Cu@PANI nanoparticles can be used as a photoacoustic probe activated by the tumor microenvironment to monitor the rate of tumor growth.
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Figure 2.
Photoacoustic imaging of tumor microenvironment activation in tumor-bearing mice.

Photoacoustic imaging (above) and corresponding photoacoustic signal intensity (bottom) obtained after Fe-Cu@PANI nanoparticles were injected into the tumor site of mice at different periods (days) of tumor growth in tumor-bearing mice ).

The author also used the 4T1 tumor-bearing mouse model to evaluate the effect of Fe-Cu@PANI nanoparticles as a photothermal agent for tumor PTT.

The results show that the combination of Fe-Cu@PANI nanoparticles and laser irradiation has a significant inhibitory effect on tumor growth.

After 4 days of treatment, the tumor tissue almost completely disappeared, and the tumor did not recur in the following 12 days.

Figure 3.
Fe-Cu@PANI nanoparticles are used for PTT of tumors in tumor-bearing mice.

(A) Thermal imaging of the tumor site injected with Fe-Cu@PANI nanoparticles or PBS with 808-nm laser irradiation; (B) Photos of four groups of tumor-bearing mice receiving different treatments at 0, 8, and 16 days ; (C) The temperature change of tumor tissue in tumor-bearing mice receiving different treatments.

(D) Changes in tumor volume of tumor-bearing mice with treatment time (days); (E) Changes in body weight of tumor-bearing mice with treatment time (days); (F) Tumor tissues of tumor-bearing mice dissected after 16 days of treatment Photo; (G) H&E staining of the heart, liver, spleen, lung and kidney tissues of tumor-bearing mice receiving different treatments was dissected 16 days after treatment.

In summary, this study prepared a kind of iron and copper co-doped polyaniline nanoparticles (Fe-Cu@PANI), and found that the Cu(II) in the nanoparticles can undergo redox reactions in the presence of GSH, resulting in The etching of the nanoparticles is accompanied by a red shift of the absorption spectrum of the nanoparticles from the visible light region to the near-infrared light region.

Therefore, Fe-Cu@PANI nanoparticles can not only be used as photoacoustic probes for accurate diagnosis of tumors in GSH photoacoustic imaging in vivo, but also can be used as an activatable photothermal agent for tumor-targeted PTT.

This thesis is the result of independent completion by Guangxi Normal University.

Doctoral student Wang Shulong is the first author of the paper, and Professor Shulin Zhao and Professor Liangliang Zhang are the co-corresponding authors of this paper.

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