Three-dimensional (3D) pancreatic β-cell models reveal insulin-secretion enhancing potential of green synthesized silver nanoparticles

Diabetes is one of the rapidly increasing chronic diseases in the world, and according to International Diabetes Federation data, it is estimated to affect approximately 537 million people worldwide. This rate corresponds to 10 % of the world's population and this number is expected to increase further in the coming years (Hossain et al., 2024). Diabetes not only causes blood sugar levels to rise uncontrollably, but can also lead to serious complications such as heart disease, kidney failure, blindness and nerve damage. The fact that diabetes has become such a common and serious health problem necessitates the development of new and more effective treatment methods (Deshpande et al., 2008). Treatments used today generally focus on controlling blood sugar levels with lifestyle changes and medications; However, studies on innovative approaches such as stem cell therapy, biotechnology-based new insulin types and artificial pancreas continue. Scientific research in this field is of great importance in improving patients' quality of life and reducing the burden of diabetes on global health. In this context, nanoparticle technology has emerged as a promising field in diabetes treatment in recent years (Hajivalizadeh et al., 2024; Kumar et al., 2024; Sena et al., 2010).

Nanoparticles increase treatment effectiveness and reduce the risk of side effects by enabling the drug to be transported to targeted areas in the body. In particular, insulin carrier systems are developed thanks to nanoparticle-based approaches, thus providing controlled and long-term release of insulin. Additionally, studies are ongoing on the protection and renewal of pancreatic beta cells using nanoparticles. These innovative treatment methods have significant potential in preventing complications of diabetes and improving patients' quality of life. The developments of nanotechnology-based treatments in the field of diabetes once again reveal the necessity of the scientific world to produce new solutions for the management of this chronic disease (Andreadi et al., 2024; He et al., 2021; Verma and Dahiya, 2024).

Considering the potential use of metal nanoparticles in the treatment of chronic diseases such as diabetes, it is of great importance to produce these nanoparticles in an environmentally friendly and safe manner. For example, green synthesis of gold and silver nanoparticles with plant extracts offers a low-cost, rapid and sustainable method. Nanoparticles produced by this method can be safely used in biomedical applications, reduce the risk of toxicity and cause less damage to the environment. In this context, green synthesis of metal nanoparticles is considered as a critical step in terms of both environmental protection and the development of advanced technologies in the biomedical field (Malik et al., 2023; Radulescu et al., 2023).

Plant extracts function as bioreducts in the reduction of metal ions thanks to the polyphenols, flavonoids, alkaloids, tannins and other antioxidant compounds they contain. Metal ions are transformed into metal nanoparticles by interacting with these natural compounds (Kumar et al., 2016). In this process, the plant compounds reduce the metal ions and also help stabilise the nanoparticles. Nanoparticles tend to aggregate during the synthesis process, which can make it difficult to maintain the desired size and properties. Plant extracts, thanks to the bioactive substances they contain, form a protective coating around the nanoparticles, stabilizing them and preventing agglomeration. This ensures that nanoparticles are obtained in homogeneous and controlled sizes (Elemike et al., 2019; Jaison et al., 2023). Green synthesis using plant extracts does not require toxic chemicals and energy-intensive conditions such as high temperature or pressure. This results in an environmentally benign, sustainable and biocompatible nanoparticle synthesis. This process with plant extracts is carried out using water-based solutions and waste generation is kept to a minimum, offering a less environmentally harmful method. Plant extracts are derived from sources that are abundant in nature and allow nanoparticle synthesis without the need for costly chemicals. In particular, the use of plant materials such as agricultural waste, leaves, bark and fruit extracts makes this process economically advantageous (Osman et al., 2024).

Cherry stems offer various biological effects due to their content of flavonoids, tannins, potassium salts, organic acids, coumarine, and antioxidants. Their most well-known property is their diuretic effect, which makes them a supportive treatment for kidney and urinary tract disorders. Cherry stem teas are widely consumed to alleviate urinary tract infections, reduce edema, and prevent the formation of kidney stones (Babotă et al., 2021). In addition, thanks to the bioactive compounds found in cherry stems, such as flavonoids and tannins, they help prevent cell damage by neutralizing free radicals, thus acting as an antioxidant, anti-inflammatory, and anti-aging herb (García-Villegas et al., 2024; Afonso et al., 2020).

The objective of this study is to examine the potential of silver nanoparticles synthesized using cherry stem extract on enhancing beta-cell functionality and facilitating insulin release in INS-1 and RIN-m5F 3D pancreatic β-cell models, through their antioxidant properties.

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