Effectiveness of Chitosan Nanoparticles as a Radioprotective Agent Against Gamma-Induced Changes in the Histology and Biochemistry of Parotid Glands

Nanoscience Chemistry Bioengineering Biochemistry Oncology Life Sciences Medicine
chitosan nanoparticles radioprotection parotid glands oxidative stress survival rate

Cancer is one of the leading causes of death worldwide. Radiotherapy, as a crucial method for cancer treatment, effectively kills cancer cells but also damages normal tissues, especially sensitive tissues such as salivary glands. The oxidative stress and inflammatory reactions induced by radiotherapy are the primary causes of salivary gland dysfunction. Therefore, finding radioprotective agents that can mitigate the side effects of radiotherapy and protect normal tissues has become a hot topic in current research.

Chitosan, a biopolymer extracted from the shells of crustaceans, possesses antioxidant, anti-inflammatory, and cell growth-promoting properties. In recent years, chitosan nanoparticles (CS NPs) have garnered significant attention due to their potential in biomedical applications, particularly in the field of radioprotection. However, the mechanisms by which chitosan nanoparticles alleviate radiotherapy-induced damage to salivary glands are not yet fully understood. Thus, this study aims to investigate whether chitosan nanoparticles can mitigate the histological and biochemical effects of radiotherapy on salivary glands and evaluate their potential as radioprotective agents.

Source of the Paper

This research was conducted by a team of researchers from Egypt, Jordan, and Saudi Arabia, with key authors including Ibrahim Y. Abdelrahman, Omayma M. Meabed, and Ali Shamaa, among others. The research team is affiliated with institutions such as the Egyptian Atomic Energy Authority, Beni-Suef University, and Kafr Elsheikh University. The paper was accepted by the journal Bionanoscience on March 13, 2025, and published in the same year.

Research Process

1. Synthesis and Characterization of Chitosan Nanoparticles

The researchers first synthesized chitosan nanoparticles. The specific steps included dissolving chitosan powder in a 2% acetic acid solution, adding 91% isopropanol, and treating it with gamma radiation to halt free radical generation. The synthesized nanoparticles were characterized using high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and dynamic light scattering (DLS). The results showed that the nanoparticles had an average diameter of 58.45±1.5 nm and a zeta potential of 29.8 mV, indicating good stability.

2. Animal Model and Experimental Design

The study used 45 adult male albino rats, divided into three groups: control group (15 rats), radiotherapy group (15 rats), and chitosan nanoparticle-treated group (15 rats). The radiotherapy and treated groups were exposed to 15 Gy of gamma radiation on the head, while the treated group received 200 mg/kg of chitosan nanoparticles orally daily, starting 2 days before radiotherapy and continuing for 7 days post-radiotherapy. Survival rates were recorded during the experiment, and parotid gland tissues were collected for further analysis at the end of the study.

3. Biochemical Marker Detection

The researchers measured oxidative stress markers (e.g., malondialdehyde, MDA), antioxidant enzyme activity (e.g., superoxide dismutase, SOD, and catalase, CAT), inflammatory factors (e.g., tumor necrosis factor, TNF-α, and interleukin, IL-6), and allergy markers (e.g., histamine and immunoglobulin E, IgE) in the serum of rats from each group. The results showed that MDA levels significantly increased in the radiotherapy group, while SOD and CAT activities significantly decreased, indicating severe oxidative stress induced by radiotherapy. In the chitosan nanoparticle-treated group, MDA levels decreased, and SOD and CAT activities partially recovered, although they did not return to control levels.

4. Histological and Immunohistochemical Analysis

Using immunohistochemical techniques, the researchers detected the expression of proliferating cell nuclear antigen (PCNA) in parotid gland tissues. The results showed that PCNA expression significantly increased in the radiotherapy group, indicating that radiotherapy promoted cell proliferation. In the chitosan nanoparticle-treated group, PCNA expression further increased, suggesting that chitosan nanoparticles have a cell regeneration-promoting effect.

Main Results

  1. Synthesis and Characterization of Chitosan Nanoparticles: The synthesized nanoparticles exhibited uniform size distribution and good stability, making them suitable for biomedical applications.
  2. Survival Rate: The survival rate of rats in the radiotherapy group was 20%, while it increased to 60% in the chitosan nanoparticle-treated group, indicating that chitosan nanoparticles significantly improved survival rates post-radiotherapy.
  3. Biochemical Markers: Chitosan nanoparticles partially alleviated oxidative stress and inflammatory reactions induced by radiotherapy, although their effects did not fully restore normal levels.
  4. Histological Analysis: Chitosan nanoparticles promoted cell regeneration in parotid gland tissues after radiotherapy, demonstrating their potential to protect salivary gland function.

Conclusion and Significance

This study demonstrates that chitosan nanoparticles, as a radioprotective agent, can effectively mitigate radiotherapy-induced damage to salivary glands and improve the survival rates of experimental animals. Their mechanism of action may be related to their antioxidant, anti-inflammatory, and cell regeneration-promoting properties. These findings provide important experimental evidence for the development of novel radioprotective agents and have potential clinical applications.

Research Highlights

  1. Innovation: This study is the first to systematically evaluate the protective effects of chitosan nanoparticles on salivary glands during radiotherapy, filling a research gap in this field.
  2. Interdisciplinary Approach: The research integrates multiple disciplines, including nanotechnology, radiobiology, and immunology, showcasing the broad potential of chitosan nanoparticles in biomedical applications.
  3. Clinical Application Prospects: The results provide a theoretical foundation for developing radioprotective agents based on chitosan nanoparticles, which may be applied in clinical radiotherapy to reduce side effects in patients.

Other Valuable Information

Although chitosan nanoparticles show promising results in mitigating the side effects of radiotherapy, their mechanisms of action require further investigation. Future research could explore the combined use of chitosan nanoparticles with other antioxidants or anti-inflammatory drugs to enhance their radioprotective effects. Additionally, the research team plans to conduct clinical trials to verify the safety and efficacy of chitosan nanoparticles in humans.

Through this study, the potential of chitosan nanoparticles as radioprotective agents has been preliminarily validated, offering new insights and tools for future cancer treatment.