The Team Of Chongqing Medical University Created A Silica Nano-messenger To Bring New Hope To The Treatment Of Cerebral Ischemia-reperfusion Injury

"For the study of stroke, there are also some personal factors. My father died suddenly because of a stroke, and it was also because of this disease that I couldn't see my father for the last time. This has always been a great regret in my heart. So I can Some research in this direction is also a comfort to myself in my heart." Associate Professor Wang Jianwei of Chongqing Medical University said.

Click to genghis khan cistanche for ischemia-reperfusion injury

Recently, he and his collaborators designed a unique "nano-messenger", which can simultaneously deal with the two pathogenic mechanisms of inflammation and oxidative stress during reperfusion injury and can be loaded with endogenous drugs to target the treatment of ischemia The penumbra area has the advantages of significant curative effect and high safety.

In detail, in the study, they used isothiocyanate fluorescein-labeled silica (SiO2) nanospheres as the core carrier and loaded anion delivery body polyacrylic acid (PAA, Polyacrylic acid) on its surface to synthesize SiO2@PAA nanospheres. The endogenous therapeutic agent's melatonin (MT, Melatonin) and acetylcholine (acetylcholine, ACh) were sequentially loaded, and after connecting the anti-C5a aptamer (aC5a) with targeting effect, the nanomedicine——SiO2@ PAA-MT/ACh-aC5a.

The controllable release of MT and ACh can be achieved through acid response in the low pH microenvironment of cerebral ischemia. Among them, MT, as an antioxidant, can remove the excessively produced reactive oxygen species in the ischemic penumbra region, to alleviate the damage caused by oxidative stress.

ACh can bind to the α7 nicotinic acetylcholine receptor (α7nAChR) on microglia, thereby activating the cholinergic anti-inflammatory pathway, promoting the polarization of microglia to the anti-inflammatory M2 phenotype, thereby reducing the release of inflammatory factors, thereby improving the damage caused by the inflammatory response.

Based on the above strategies, SiO2@PAA-MT/ACh-aC5a nanospheres can play a synergistic therapeutic effect, significantly reduce the inflammatory response and oxidative stress level after cerebral ischemia-reperfusion, and improve the ischemic brain damage by reducing neuron death. stroke prognosis. For the treatment of cerebral ischemia-reperfusion, the drug has a very positive role in promoting it.

It is understood that stroke (stroke) is one of the major diseases with high morbidity and mortality worldwide. In domestic statistical data, it is the disease that ranks first in terms of morbidity, mortality, and disability. Among them, ischemic stroke accounts for more than 80% of all cerebrovascular diseases.

Although after ischemia, tissue and organ functions can be restored by reperfusion. However, more and more studies have found that during the treatment of ischemic diseases, the main factor causing tissue damage is not ischemia itself, but a large number of oxygen-free radicals and inflammatory factors produced by reperfusion after the blood supply is restored. , leading to apoptosis or necrosis of cells, resulting in tissue and organ damage, that is, "ischemia-reperfusion injury".

Cerebral ischemia-reperfusion injury is a more serious and common clinical syndrome faced by ischemic stroke patients after the restoration of blood supply. For the control of reperfusion injury, a clear solution has not yet been found, and it is against this background that this study was carried out.

According to reports, the nano-drugs constructed this time can be loaded with multiple drugs at the same time to realize the synergistic treatment of multiple drugs. It not only greatly improves the effect of drug treatment, but also minimizes the toxic and side effects on normal tissues.

Wang Jianwei said: "In addition, our drug synthesis cost is low, the synthesis principle is simple, and it is easy to achieve large-scale production. These determine that our nano-medicine has important application value in clinical treatment, and it is expected to be used as a first-line treatment. Treatment of cerebral ischemia-reperfusion injury."

In addition, the nanosystem is a platform for drug delivery and release. Through the change of drug loading, it can also realize the treatment of other diseases, and it is universal for cancer, rheumatoid arthritis, and other diseases.

Looking back on the research process, Wang Jianwei said: "What impressed me the most was my experience of building an animal model of reperfusion injury with my students. Although I have done a lot of animal experiments with mice, with large It is the first time that rats are doing brain experiments, and in this process, what is different from usual is the transformation of roles. 

The students are more proficient in animal experiments than me, and they are the ones who teach me. And let them Integrating learning into teaching is also the core of Feynman's learning method (Editor's Note: A teaching method originated from the Nobel Prize winner Richard Feynman (Richard Feynman)).

Wang Jianwei continued: "The hard work of the students also left a deep impression on me. If the experiment failed, they would not eat dinner. They must insist on completing the experiment first. Good output."

A few days ago, a related paper entitled "Acetylcholine and Melatonin by C5a-Targeted Aptamers Effectively Attenuates Reperfusion Injury of Ischemic Stroke" (Acetylcholine and Melatonin by C5a-Targeted Aptamers Effectively Attenuate Reperfusion Injury of Ischemic Stroke) was published on Advanced Functional Materials [1].

Xinyu Xiao is the first author; Wang Jianwei, Associate Professor Peng Qiling, and Associate Professor Jiang Ning from the same school are the co-corresponding authors.

At present, in cell models and animal models, this nano-drug has been proven to have a good effect and good biological safety.

Next, they are about to conduct clinical trials. "Our school itself has many affiliated hospitals with good conditions for clinical experiments. We are currently planning to cooperate with clinicians to push nano-medicines into clinical applications as soon as possible." Wang Jianwei said.

How Cistanche extract can help improve brain disorders？

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References:

1. Xiao, X., Gao, Y., Liu, S., Wang, M., Zhong, M., Wang, J., ... & Peng, Q. (2023). A “Nano‐Courier” for Precise Delivery of Acetylcholine and Melatonin by C5a‐Targeted Aptamers Effectively Attenuates Reperfusion Injury of Ischemic Stroke. Advanced Functional Materials, 2213633.