Conjugated Human Serum Albumin/Gold-Silica Nanoparticles as Multifunctional Carrier of a Chemotherapeutic Drug

We report the design and development of a novel multifunctional nanostructure, RB-AuSiO₂_HSA-DOX, where tri-modal cancer treatment strategies-photothermal therapy (PTT), photodynamic therapy (PDT), chemotherapy-luminescent properties and targeting are integrated into the same scaffold. It consists of a gold core with optical and thermo-plasmonic properties and is covered by a silica shell entrapping a well-known photosensitizer and luminophore, Rose Bengal (RB). The nanoparticle surface was decorated with Human Serum Albumin (HSA) through a covalent conjugation to confer its targeting abilities and as a carrier of Doxorubicin (DOX), one of the most effective anticancer drugs in clinical chemotherapy. The obtained nanostructure was fully characterized through transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV-visible spectroscopy, with a homogeneous and spherical shape, an average diameter of about 60 nm and negative ζ-potential value Singlet oxygen generation and photothermal properties were explored under green light irradiation. The interaction between DOX-HSA anchored on the nanoplatform was investigated by fluorescence spectroscopy and compared to that of DOX-HSA, pointing out different accessibility of the drug molecules to the HSA binding sites, whether the protein is free or bound to the nanoparticle surface. To the best of our knowledge, there are no studies comparing a drug-HSA interaction with that of the same protein anchored to nanoparticles. Furthermore, the uptake of RB-AuSiO₂_HSA-DOX into MDA-MB-231 mammary cells was assessed by confocal imaging, highlighting-at early time of incubation and as demonstrated by the increased DOX luminescence displayed within cells-a better internalization of the carried anticancer drug compared to the free one, making the obtained nanostructure a suitable and promising platform for an anticancer multimodal approach.