ALBA Synchrotron

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 Synchrotron, devised 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.
The findings demonstrate a marked improvement compared to previous methods. For example, nanoparticles coated with pNIPAM displayed no shift in their optical properties under near-infrared laser irradiation, while those coated with pAA showed a minimal 7-nanometer change. This contrasts sharply with the significant 50-nanometer shift observed with PEG coatings, marking a 50-fold increase in stability for pNIPAM and a 7-fold increase for pAA compared to PEG. The increased stability under laser exposure opens up the potential for gold nanoparticles to be used as more reliable photothermal agents over extended periods in clinical settings, which could potentially lead to more effective and sustained cancer treatments.
Synchrotron light analysis, notably small-angle X-ray scattering (SAXS) at the NCD-SWEET beamline at ALBA, was essential to confirm the precise uniformity of the thin nanogels as well as their adherence to the nanoparticles. This technique allowed the team to verify that the protective layer did not interfere with the nanoparticles' anisotropic properties and thus provided the structural insights needed to achieve the delicate balance between protection and functionality.
Once the stability issues are resolved, this research not only paves the way for clinical exploration of cancer treatment with gold nanoparticles, but also for other biomedical applications, such as the polymerization of nanogels around proteins in skin wound healing.
Small-angle X-ray scattering (SAXS) patterns of anisotropic gold nanoparticles (AuNPs). On the left, the SAXS profile of rod-shaped AuNPs is shown, with the inset displaying a TEM image of the rod (2.8 nm thickness) and a schematic illustration of the nanogel coating. On the right, the SAXS pattern of a nanostar is presented, highlighting contributions from both the overall size and the individual star spikes. The inset shows a TEM image of the nanostar with characteristic dimensions of 4.6 nm and 6.8 nm for the star arms.