From Nature to molecular-diagnosis: design of bio-based photoacoustic nanoprobes

Photoacoustic Imaging (PAI) is an exciting new modality that uses non-ionizing radiation for real-time imaging with high spatial resolution and penetration depth. A broad range of application areas for molecular PAI have been identified, including oncology, neuroscience and cardiovascular diseases; so far basic research studies and preliminary clinical trials have focused primarily on detection, staging and therapeutic monitoring in cancer. The development of bio-inspired NIR responsive nanomaterials plays a key role in improving sensitivity and signal-to-noise ratio in photoacoustic imaging. To date, a promising approach relies on the green synthesis of nanoparticles starting from natural or endogenous materials as a source of contrast. Among those, eumelanins, hydrophobic natural pigments, are emerging as a powerful organic component for developing biologically active materials because of their numerous biological functions, such as photo-protection, photosensitization, free radical quenching, metal ion chelation and even intrinsic antimicrobial behavior. They combine safety with marked antioxidant features as well as a broad band of absorption in the visible and near infrared (NIR) regions and thus can be potentially applied in Photoacoustic Imaging. To date, several melanin-based probes have been reported with specific properties for PAI, however, poor solubility of eumelanins in biological fluids as well as poor contrast of PA signal, if compared to other contrast agents must be addressed. Solubility issues are usually addressed by conjugation of the biopolymer onto a foreign matrix, made of either organic or inorganic materials. Among those, silica stands as an outstanding, safe and biocompatible choice to ensure chromophore stability as well as an improvement of PA signal amplitude, through confinement effect. Furthermore, Silica allows easy functionalization to guarantee active targeting, as well as long circulation times. Following a bioinspired approach, we designed a prototype of PA eumelanin-based hybrid nanoprobe constructed by Redox interaction of eumelanin silica hybrid nanoparticles with Ag+ ions. These nanoplatforms proved high stability towards aggregation and high biocompatibility and PA contrast enhancement.