Aerosol-synthesized siliceous nanoparticles: Impact of morphology and functionalization on biodistribution

Introduction: Siliceous nanoparticles (NPs) have been extensively studied in nanomedicine due to their high biocompatibility and immense biomedical potential. Although numerous technologies have been developed, the synthesis of siliceous NPs for biomedical applications mainly relies on a few core technologies predominantly intended to produce spherical-shaped NPs. Methods: In this context, the impact of different morphologies of siliceous NPs on biodistribution in vivo is limited. In the present study, we developed a novel technique based on an aerosol silane reactor to produce sintered silicon NPs of similar size but different surface areas due to distinct spherical subunits. Silica-converted particles were functionalized for radiolabeling with copper-64 ( ⁶⁴ Cu) to systematically analyze their behavior in the passive targeting of A431 tumor xenografts in mice after intravenous injection. Results: While low nonspecific uptake was observed in most organs, the majority of particles were accumulated in the liver, spleen, and lung. Depending on the morphologies and functionalization, significant differences in the uptake profiles of the particles were observed. In terms of tumor uptake, spherical shapes with lower surface areas showed the highest accumulation and tumor-to-blood ratios of all investigated particles. Conclusion: This study highlights the importance of shape and fuctionalization of siliceous NPs on organ and tumor accumulation as significant factors for biomedical applications.