Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles

Nanoparticles are a promising solution for delivery of a wide range of medicines and vaccines. Optimizing their design depends on being able to resolve, understand, and predict biophysical and therapeutic properties, as a function of design parameters. While existing tools have made great progress, gaps in understanding remain because of the inability to make detailed measurements of multiple correlated properties. Typically, an average measurement is made across a heterogeneous population, obscuring potentially important information. In this work, we develop and apply a method for characterizing nanoparticles with single-particle resolution. We use convex lens-induced confinement (CLiC) microscopy to isolate and quantify the diffusive trajectories and fluorescent intensities of individual nanoparticles trapped in microwells for long times. First, we benchmark detailed measurements of fluorescent polystyrene nanoparticles against prior data to validate our approach. Second, we apply our method to investigate the size and loading properties of lipid nanoparticle (LNP) vehicles containing silencing RNA (siRNA), as a function of lipid formulation, solution pH, and drug-loading. By taking a comprehensive look at the correlation between the intensity and size measurements, we gain insights into LNP structure and how the siRNA is distributed in the LNP. Beyond introducing an analytic for size and loading, this work allows for future studies of dynamics with single-particle resolution, such as LNP fusion and drug-release kinetics. The prime contribution of this work is to better understand the connections between microscopic and macroscopic properties of drug-delivery vehicles, enabling and accelerating their discovery and development

Non-wettable, Oxidation-Stable, Brightly Luminescent, Perfluorodecyl-Capped Silicon Nanocrystal Film

Here we describe for the first time the synthesis of colloidally stable, brightly luminescent per­fluoro­decyl-capped silicon nano­crystals and compare the properties of solutions and films made from them with those of their per­hydro­decyl-capped relatives. The per­fluoro­decyl capping group compared to the per­hydro­decyl capping group yields superior hydro­phobicity and much greater resistance to air oxidation, the enhanced electron-withdrawing character induces blue shifts in the wavelength of photo­lumin­escence, and the lower-frequency carbon–fluorine stretching modes disfavor non-radiative relaxation pathways and boost the absolute photo­lumin­escence quantum yield. Together these attributes bode well for advanced materials and biomedical applications founded upon per­fluoro­decyl-protected silicon nanocrystals

Non-wettable, oxidation-stable, brightly luminescent, perfluorodecyl-capped silicon nanocrystal film

Here we describe for the first time the synthesis of colloidally stable, brightly luminescent perfluorodecyl-capped silicon nanocrystals and compare the properties of solutions and films made from them with those of their perhydrodecyl-capped relatives. The perfluorodecyl capping group compared to the perhydrodecyl capping group yields superior hydrophobicity and much greater resistance to air oxidation, the enhanced electron-withdrawing character induces blue shifts in the wavelength of photoluminescence, and the lower-frequency carbon-fluorine stretching modes disfavor non-radiative relaxation pathways and boost the absolute photoluminescence quantum yield. Together these attributes bode well for advanced materials and biomedical applications founded upon perfluorodecyl-protected silicon nanocrystals