Research Assistant Professor University of New Mexico, United States
Introduction: Organ-targeting is currently a main challenge in drug delivery. A major downside to administering drugs or carrier-loaded drugs is the non-specific uptake by the liver and spleen, thus lowering the efficacy and promoting side effects. In the quest for specific-organ targeting systems, we are studying the overlooked nanotopography effects of silica-based inorganic nanoparticles to guide organ-specific preferential accumulation. Our capacity to control the colloidal mesoporous silica nanoparticle morphology allows for fine-tuning of the surface features, namely the nanotopography. In this presentation, we will show how colloidally stable mesoporous silica nanoparticles with dendritic structures of different architectures (dense, light, stellar), and their surface chemistry affect their colloidal stability, interaction with lipids, cell uptake kinetics, hemolytic activity, and in vivo properties including blood circulation time and biodistribution.
Materials and
Methods: The fabrication of the nanodendrites follows a procedure we recently published in ACS Nano (Noureddine et al. 2023) where a biphasic reactor is used to fine-tune the structure of silica particles made with a templated self-assembly of silica monomers. The yielded samples remain stable for several years when stored in ethanol. The nanodendrites are then characterized and exposed to cells and mice to assess the evolution of their behavior in the function of the nanotopography. A matrix of techniques is used to characterize the nanoparticles including electron microscopy, dynamic light scattering, zeta potential and their in vitro behavior by flow cytometry, confocal microscopy, and cell viability assays, not to mention the hemolysis assay for ex vivo interactions with red blood cell membrane. As for in vivo work, mice were intravenously injected with 10 mg/mg far red dyed fluorescent nanoparticles with increasing density of silica structure (from dense dendrites to light dendrites). Their biodistribution was assessed by in vivo imaging spectrometry (IVIS) upon organ harvesting after 24 h injection (IACUC protocol 22-201155-HSC).
Results, Conclusions, and Discussions: First, we confirmed that we are capable of creating a series of nanodendrites with evolutionary structure density by a simple fine-tuning of the synthetic conditions. Electron microscopy shows the physical structure is correlated with the colloidal size measured by dynamic light scattering. The versatility of this procedure is harnessed to create the structures in both positive and negative charges. We found that nanotopography dictates the interaction with synthetic lipids in silico, which was then translated to the cellular lipid membrane. The nanotopography was also a key factor in the hemolytic activity of red blood cells, prostate cell uptake kinetics, and most notably in the circulation half-life of the nanoparticles in mice blood and their organ-oriented accumulation. We conclude that the inorganic nanoparticle surface nanotopography, which has been an overlooked factor, is an important feature to consider in the biomedical application of nanotechnology.
Acknowledgements (Optional): University of New Mexico Center for Metals in Biology and Medicine CMBM via NIH NIGMS grant P20 GM130422
