Nature-inspired design: bio-based photoacoustic nanoprobes

One of the emerging research areas at the convergence of physical science, chemistry, engineering, and life science is the development of theranostic nanoagents that integrate therapy and diagnosis for cost-effective precision medicine. Among currently available imaging methodologies, photoacoustic imaging (PAI) is an exciting new modality that uses non-ionizing radiation for real-time imaging with high spatial resolution and penetration depth. Furthermore, PAI could be easily combined with poor invasive cancer therapies, such as Phototermal Ablation. The development of bio-inspired NIR responsive nanomaterials plays a key role in improving sensitivity and signal-to-noise ratio in PAI. To this purpose a promising approach relies on the green synthesis of nanoparticles starting from natural or endogenous materials as a source of contrast. To date, several melanin-based probes have been reported with specific properties for PAI, however, poor solubility in biological fluids as well as poor contrast of photoacoustic signal, if compared to other contrast agents must be addressed. By mimicking natural melanin we reported the first example of stable monodispersed hybrid nanoparticles (MelaSil-NPs) made up of eumelanin biopolymer intimately integrated into a silica matrix. One-pot in-situ templated synthesis strategy was carried out where all components, form together and influenced each other. In particular, metal chelating and reducing properties of melanins towards transition metal ions were exploited to obtain Ag ions reduction (MelaSil_Ag), while at the same time controlling the growth of in-situ generated silver-nanoclusters. Nanostructured SiO2 was employed as templating agent for DHICA polymerization to melanin and a core-shell architecture was obtained, with enhanced photoacoustic signal. Furthermore, hybrid nature of the material allowed a fine control of morphology and stability to aggregation, ensuring cellular uptake and ultimately leading to promising probes for multimodal imaging in cancer diagnosis and therapy.