Periodic Reporting for period 1 - SUNSET (Targeting cancer with multi-engineered selenium nanoparticles (SeNPs): Development of a biocompatible nanocomposite for targeted gene therapy in BRAF-mutated resistant melanoma.)
Reporting period: 2023-06-01 to 2025-05-31
Melanoma is one of the most aggressive forms of cancer responsible for the majority of skin cancer-related deaths. The Global Cancer Observatory reports that in 2022, over 150,000 new cases were reported in Europe, and the numbers continue to rise. When possible, surgery represents the first therapeutic option. Moreover, in the most severe cases, patients undergo adjuvant therapies to reduce the risk of metastasis and/or relapse. However, current treatments are not always effective, and patients with this type of melanoma often experience recurrence. The metastatic disease, indeed, is still responsible for 90% of deaths. It has been demonstrated that mutations in the BRAF gene are present in about 66% of these patients. Due to this, several targeted therapies have been developed to block the mutated BRAF protein, and some drugs are now in clinical use. Despite initial effectiveness, many patients eventually develop resistance to these treatments overtime. Thus, finding new strategies to overcome this resistance is a major focus of ongoing melanoma research.
Nanotechnology has been proven a promising tool for several biomedical applications, including targeted cancer therapy. The SUNSET project aimed to develop a new nanoplatform based on multi-engineered selenium nanoparticles for gene targeting therapy of resistant melanoma. Here, selenium-based nanoparicles (SeNPs) were functionalized with a small interfering RNA against BRAF (siBRAF) and covered with hyaluronic acid (HA) to selectively enter melanoma cells. The nanosystem aimed to block the production of the BRAF protein by overcoming the resistance of BRAF mutated melanoma to the current treatments. To purpose this objectives green chemistry procedures were exclusively used in the preparation of these SeNPs.
Nanotechnology has been proven a promising tool for several biomedical applications, including targeted cancer therapy. The SUNSET project aimed to develop a new nanoplatform based on multi-engineered selenium nanoparticles for gene targeting therapy of resistant melanoma. Here, selenium-based nanoparicles (SeNPs) were functionalized with a small interfering RNA against BRAF (siBRAF) and covered with hyaluronic acid (HA) to selectively enter melanoma cells. The nanosystem aimed to block the production of the BRAF protein by overcoming the resistance of BRAF mutated melanoma to the current treatments. To purpose this objectives green chemistry procedures were exclusively used in the preparation of these SeNPs.
As first objective, SeNPs were prepared exploiting a one-pot green, chemical synthesis. This procedure provided the particles with desired physicochemical properties. The biological activity of the system was investigated in terms of cytotoxicity and gene silencing capacity. The data shown that the lockdown of both the messenger RNA (mRNA) and the protein were achieved in melanoma cell lines.
Moreover, an injectable hydrogel was also obtained using the natural derived polymer and an antioxidant molecule, as main components of the hydrogel. The formulation was proven biocompatible in the used range of concentration, in the tested cell lines. Lastly, the desired nanocomposite was obtained by integrating the particles in the hydrogel matrix.
Moreover, an injectable hydrogel was also obtained using the natural derived polymer and an antioxidant molecule, as main components of the hydrogel. The formulation was proven biocompatible in the used range of concentration, in the tested cell lines. Lastly, the desired nanocomposite was obtained by integrating the particles in the hydrogel matrix.
The SUNSET project produced a fully green chemistry route for the preparation of a functionalized selenium based nanoplatform to potentially use in cancer melanoma therapy. Given the simplicity of the procedures used, the safety of all materials involved, and the absence of organic or toxic waste generated during the synthsis process, the nanoplatform is well-suited for scale-up without posing environmental risks. Therefore, this nanoplatform could have significant industrial impact, as pharmaceutical companies might adapt the optimized process to similar materials that currently rely on organic solvents and/or toxic reagents. Moreover, in a middle-long-term, patients with a poor prognosis, that undergo surgical resection of melanoma could benefit from the treatment with such nanosystem.