General synthesis of silica-based yolk/shell hybrid nanomaterials and in vivo tumor vasculature targeting

Multifunctional yolk/shell-structured hybrid nanomaterials have attracted increasing interest as theranostic nanoplatforms for cancer imaging and therapy. However, because of the lack of suitable surface engineering and tumor targeting strategies, previous research has focused mainly on nanostructure design and synthesis with few successful examples showing active tumor targeting after systemic administration. In this study, we report the general synthetic strategy of chelator-free zirconium-89 (⁸⁹Zr)-radiolabeled, TRC105 antibody-conjugated, silica-based yolk/shell hybrid nanoparticles for in vivo tumor vasculature targeting. Three types of inorganic nanoparticles with varying morphologies and sizes were selected as the internal cores, which were encapsulated into single hollow mesoporous silica nanoshells to form the yolk/shell-structured hybrid nanoparticles. As a proof-of-concept, we demonstrated successful surface functionalization of the nanoparticles with polyethylene glycol, TRC105 antibody (specific for CD105/endoglin), and ⁸⁹Zr (a positron-emitting radioisotope), and enhanced in vivo tumor vasculature-targeted positron emission tomography imaging in 4T1 murine breast tumor-bearing mice. This strategy could be applied to the synthesis of other types of yolk/shell theranostic nanoparticles for tumor-targeted imaging and drug delivery.