Structural Characterization of Self-Assembling Hybrid Nanoparticles for Bisphosphonate Delivery in Tumors

Hybrid self-assembling nanoparticles (hsaNPs) encapsulating bisphosphonates (BPs) recently showed very promising results in preclinic experiments for the treatment of brain tumor. However, the poor knowledge on the architecture of hybrid nanovectors is certainly one of the main reasons hampering further clinical and industrial development of these technologies. Here we propose to combine different techniques, i.e. Small Angle Neutron Scattering (SANS) and X-ray Scattering (SAXS), with cryo-Electron Transmission Microscopy (cryo-TEM) to study the architecture of the final hsaNPs as well as of the four components before the assembling process. Data analysis based on SANS and SAXS experiments, suggested a multiple compartment architecture of the final product, consisting of two bilayers sourrounding a core. Structure consisting of two shells surrounding an internal core were also observed in the cryo-TEM analysis. Such high resolution insights, also combined with size distribution and zeta potential of the NPs, provides exaustive characterization of hsaNPs encapsulating BPs, and it is aimed at supporting further their clinical and industrial development.