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Nanotechnology Now – Press Release: Nanonitrator: a new enhancer of the protective effects of inorganic nitrates, based on a swarm learning approach

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A learning-based drug combination prediction system that identified vitamin C as the optimal drug for combination with sodium nitrate.  This combination increases the bioavailability of sodium nitrate and provides a synergistic effect.  Next, the team used microencapsulation technology to prepare nanoparticles called Nanonitrators, with sodium nitrate and vitamin C as the main components.  The nanonitrator prevented tissue damage in a model of radiation-induced salivary gland injury, verifying its better efficacy than sodium nitrate alone.  CREDIT © Science China Press
A learning-based drug combination prediction system that identified vitamin C as the optimal drug for combination with sodium nitrate. This combination increases the bioavailability of sodium nitrate and provides a synergistic effect. Next, the team used microencapsulation technology to prepare nanoparticles called Nanonitrators, with sodium nitrate and vitamin C as the main components. The nanonitrator prevented tissue damage in a model of radiation-induced salivary gland injury, verifying its better efficacy than sodium nitrate alone. CREDIT © Science China Press

Abstract:
Radiotherapy is currently the main form of treatment for head and neck malignancies such as nasopharyngeal carcinoma. In the tumor radiation field, the salivary glands often undergo substantial damage after irradiation, resulting in xerostomia and a series of oral syndromes, which have a serious impact on the patient’s quality of life.

Nanonitrator: a new enhancer of the protective effect of inorganic nitrates, based on a herd learning approach

Beijing, China | Posted on May 12, 2023

In 1998, a research team led by Prof. Songlin Wang made a miniature model of a pig to simulate clinical salivary gland injuries caused by radiation in the head and neck region. This model was used in a series of studies on the mechanism of radiation-induced salivary gland injury as well as the functional reconstruction of damaged glands. The team found that exogenous inorganic nitrate supplementation can significantly protect salivary gland morphology and function from radiation injury, indicating a new way of prevention and treatment.

Most of the existing experimental studies on inorganic nitrate therapy have been based on oral administration, including the addition of nitrates to food and drinking water. Nitrates administered orally have low bioavailability, rapid metabolism, and high in vivo fluctuations, making it difficult to achieve pharmacodynamically active concentrations. To address these issues and facilitate clinical application, the team has successfully developed a drug combination prediction system based on herd studies. Using a deep learning model, the system is trained on drug pathway interaction data to build a drug pathway network. Graph convolutional neural networks are used to construct drug target networks to uncover optimal drug combinations. The system was used to successfully identify vitamin C as the optimal drug for co-administration with sodium nitrate. These findings provide new ideas and methods for co-administration of drugs, with important clinical implications for the prevention of various diseases.

From this, the optimal nitrate-to-vitamin C ratio was determined using microencapsulation technology for screening and optimization of controlled release formulations. Thus a hydrophobic nano drug named Nanonitrator was prepared, using a core material solution containing sodium nitrate, vitamin C, and chitosan 3000, while sodium carboxymethyl cellulose (Na-CMC) and pectin were used as wall materials. The core and wall materials are mixed, lyophilized, and crushed into powder form. Various pH values ​​of gastrointestinal solutions tested in vitro confirmed that the Nanonitrator is suitable in oral dosage forms.

Due to its ability to significantly enhance the signal transduction of the PI3K-Akt pathway, Nanonitrator exhibits a better effect in maintaining intracellular homeostasis than sodium nitrate alone or sodium nitrate incorporated in a physical mixture with vitamin C at equivalent oral doses. Nanonitrators reduce radiation-induced oxidative stress in salivary gland cells, reduce ROS content, maintain cellular calcium homeostasis, protect mitochondrial morphology and function, and decrease the number of apoptotic cells.

These results indicate that Nanonitrator can be developed as a new therapy with a wide range of applications, with the potential to play an important role in the prevention and treatment of associated chronic diseases. In addition, this research provides new ideas for the development of new drugs based on inorganic salts.

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Contact:
Media Contact

Be Yan
Science China Press

Expert Contact

Professor Xiaogang Wang
Engineering Medical School, Beihang University

Prof. Yuji Wang
School of Pharmaceutical Sciences, Capital Medical University

Professor Songlin Wang
Capital Medical University

Copyright © Science China Press

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The news release publisher, not 7th Wave, Inc. or Nanotechnology Now, is solely responsible for the accuracy of the content.

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