Nature Sub-Journal: The new molecular mechanism is expected to be more effective for lung cancer!

Lung cancer is a malignant disease
.
Therefore, once suffering from lung cancer, it will bring great harm to the patient's health

For example, the occurrence of lung cancer can affect the health of the bronchi; cancer cells spread and metastasize throughout the body, easily spreading to important organs, such as the brain or liver, which can cause liver dysfunction
.

Once the organ is damaged too much, it is difficult to maintain a normal life, which may be life-threatening; if the cancer is not controlled, it will continue to expand and may invade the patient’s pleura

This can cause chest pain and pleural effusion
.
When the pleural effusion is too much, it can compress the lungs, making the patient's dyspnea symptoms more serious

However, lung cancer is difficult to detect and treat because the markers of this disease are also present in other tissues

They published an article in the journal Nature Chemistry
.

In this study, scientists described and explained the ability of this molecule to target lung cancer cells, imaged and targeted them in human cancer cell lines and living mouse petri dishes
.
In their experiment, they chose an unexpected biomarker as the research object: glutathione

Glutathione is a molecule naturally produced in various tissues of the human body, but its expression is greater in lung cancer
.
They explained: “Due to the universality of glutathione, it has not been a good target for chemotherapy and other treatments

Jefferson Chan, professor of chemistry at the University of Illinois, and graduate student Melissa Lucero conducted the experiment and research together

He said: "One of the biggest problems that need to be faced when developing diagnostic tools or targeted drugs is off-target effects
.
When you give patients chemotherapy, it is like an arms race: because you are killing cancer cells, you are actually The above is killing other parts of the body, because many things are similar

The researchers adjusted the dynamic range of the molecule so that it would not react to glutathione in a healthy environment, but would react with excess glutathione produced by cancer cells

They paired the target molecule with a photoacoustic imaging agent so they could see where it reacted and verified that its target was lung cancer
.

The imaging agent reacts to the light and emits a sound signal that can be received by the ultrasonic transducer
.

Chan said: "This is a technology in which light enters sound
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Compared with traditional medical imaging, this technology has many advantages
.

This imaging technology is very powerful because of its high resolution, safety and compatibility
.
The ability to design molecular interactions, at the molecular level, it can convey a lot of information to us
.

In hospitals, handheld and laparoscopic optical equipment can be seamlessly integrated with ultrasound equipment, so we know that when we develop this technology, it will play a role in clinical applications
.
"The researchers first tested the imaging capabilities of this new molecule in a cell culture dish and found that healthy cells can be clearly distinguished from cancer cells
.

To assess the diagnostic potential, they conducted a blind study on live mice, using photoacoustic probes to determine which mice in the cohort had lung cancer tumors
.
Lucero said: "This research marks the first successful application of photoacoustic imaging to lung tissue
.
" Then, the researchers explored whether their targeting method can be used to deliver treatment directly to the site of cancer cells
.

It will eliminate the biggest disadvantage of chemotherapy and other cancer treatments: it is toxic to the entire body
.

This is a side effect of many methods of treating cancer patients, but this new type of targeted therapy can break through this obstacle and overcome the terrible side effects
.

They created a prodrug, named PARx, and combined their targeted imaging probe with a powerful chemotherapeutic drug and tested it on mice
.

They found that PARx inhibited tumor growth, while the mice showed no signs or symptoms of off-target toxicity, such as weight loss or liver damage
.

In contrast, during the three-week treatment period, the tumors of the mice in the control group but not the drug treatment increased significantly
.

Lucero said: "We have found that the use of high or frequent doses of drugs does not produce off-target effects
.

Subsequently, we did more experiments on other clinically relevant mouse models to discover and treat cancer and primary liver metastases
.
This highlights the wide application potential of this method
.
"

In the next step, they are working to further improve selectivity and detection capabilities so that they can detect micrometastasis anywhere in the body, or the spread of tiny clusters of cancer cells
.

They are also seeking to apply their methods to other biomarkers to create finely targeted molecules for other cancers
.

Jefferson Chan said: "When you target a fatal disease, such as lung cancer, if you find that you have no symptoms in the early stage, it can actually be cured
.
This early diagnosis requires finding the correct biomarkers.
Now we have the preliminary The diagnosis is successful
.
There is hope for treatment, because by using chemical means, we can combat the toxicity of these drugs so that they can be safely used to treat patients
.
"