Improved stability of gold nanoparticles for cancer therapy

A study carried out by researchers from POLYMAT-University of the Basque Country, INIFTA-Universidad Nacional de la Plata and the ALBA Synchrotron has made promising advances in the stabilization of gold nanoparticles (AuNPs) for use in cancer therapy. The work, published in the scientific journal Small, describes the synthesis of anisotropic hybrid particles of gold nanoparticles and nanogel, which overcome the challenges that have held back the clinical application of AuNPs, while maintaining their optical properties for the first time.

Gold nanoparticles are considered a powerful tool in photothermal cancer treatment due to their ability to convert light into heat, which is concentrated on tumor cells to destroy them. However, research has shown that unprotected anisotropic gold nanoparticles are prone to to undergo evaporation and condensation processes that result in the loss of their photothermal properties during the duration of the irradiation treatment. A new study, published in the scientific journal Small, presents a novel approach for stabilizing these particles while preserving their critical optical characteristics and, therefore, with the potential to improve the efficacy of cancer therapies.

Anisotropic gold nanoparticles are non-spherical photothermal particles that can be designed for thermal conversion by near-infrared irradiation, which is particularly advantageous in medical applications because of their high penetration depth in biological tissues and low toxicity to normal cells. However, their structural instability precludes prolonged therapeutic use. For this reason, previous studies have attempted to coat gold nanoparticles in gels such as polyethylene glycol (PEG). Yet, while these coatings improved stability, they also altered the unique shape and optical properties of the gold nanoparticles, significantly reducing their photothermal efficacy.

In this new study, researchers from POLYMAT-University of the Basque Country, INIFTA-La Plata National University, and the ALBA Synchrotrondevised a one-pot synthesis method that stabilizes anisotropic gold nanoparticles by coating them in an ultra thin, in situ polymeric nanogel. Using polyacrylamide (pAA) and poly-(N-isopropylacrylamide) (pNIPAM), the team achieved nanogel shells between 2–8 nanometers thick around each individual gold nanoparticle. This ultra thin coating preserved the nanoparticles’ dimensions and shape, ensuring that their unique optical and photothermal properties were unaffected. Notably, rod-shaped and star-shaped nanoparticles retained their structural integrity and optical characteristics, with rod-shaped hybrids showing particularly promising stability and efficiency for photothermal applications. The researchers also found that pNIPAM coatings offered the best protection for the nanoparticles, while pAA coatings exhibited optimal photothermal conversion efficiency.

Read more on ALBA website

New insights to advance targeted brain cancer therapy

Despite an increase in new chemotherapies, the overall prognosis for patients with glioblastoma multiforme (GBM) remains extremely poor, with just 5% of patients surviving for more than five years. This aggressive form of brain cancer is highly resistant to treatment, prompting researchers to explore new treatment avenuesRiluzole, a drug that has already been approved by the FDA to treat amyotrophic lateral sclerosis (ALS), is currently being explored as a treatment for several cancers including GBM. However, there is a need for novel drug delivery methods to enhance riluzole’s effectiveness and overcome barriers to targeted therapy, including minimizing harmful side effects in healthy cells, and maintaining the drug’s anti-cancer efficacy until it reaches tumor cells.

In this study, which was led by Tanja Dučić, scientist in the MIRAS beamline team at the ALBA Synchrotron, and published in ACS Omegaresearchers engineered carbon-based nanoparticles, or carbon dots, made of 2-acrylamido-2-methylpropanesulfonic acid (AMPS). This organic delivery system (AMPS-CDs NPs) showed biocompatibility with glioblastoma cells, and researchers were keen to test its potential to act as a nanocarrier for the drug riluzole.

Several Spanish institutions and researchers collaborated in this project, including Manuel Algarra from INAMAT2 (Institute for Advanced Materials and Mathematics), at the Public University of Navarra; Elena Gonzalez-Munoz, Maria Soledad Pino-González and Juan Soto from the University of MalagaPablo Guerra from the Institute of Molecular Biology of Barcelona (IBMB-CSIC); and Tanja Dučić from ALBA.

The study demonstrates the successful complementarity between synchrotron light and electron microscopy. By combining the MIRAS beamline and the Cryo-TEM at IBMB-CSIC, part of the Joint Electron Microscopy Center at ALBA (JEMCA), the collaboration achieved its first publication using both instruments. Pablo Guerra, coordinator of the Cryo-TEM, performed the microscope data acquisition. “Using the Cryo-TEM we confirmed the nanoparticles’ shape and size, with a diameter of 4.5-5 nm, which was impossible to observe with other methods”, says Tanja Dučić.

The nanoparticles were extensively characterized to determine their exact surface composition using techniques that included XPS (X-ray photoelectron spectroscopy) and NMR (nuclear magnetic resonance) spectroscopy, as well as cryo-transmission electron microscopy. The synthesized nanoparticles are covered in sulfonated, carboxylic, and substituted amide groups. These functional groups make the AMPS-CDs potentially suitable nanocarriers for riluzole.

Read more on ALBA website

Image: Researchers Tanja Dučić from ALBA and Pablo Guerra from IBMB-CSIC at the control room of the EM01-Cryo-TEM of the Joint Electron Microscopy Center at ALBA

Credit: JEMCA