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The development of endosomal disruptive agents is a major challenge in the field of drug delivery and pharmaceutical chemistry. Current endosomal disruptive agents are composed of polymers, peptides, and nanoparticles and have had limited clinical impact. Alternatives to traditional endosomal disruptive agents are therefore greatly needed. In this report, we introduce a new class of low molecular weight endosomal disruptive agents, termed caged surfactants, that selectively disrupt endosomes via reversible PEGylation under acidic endosomal conditions. The caged surfactants have the potential to address several of the limitations hindering the development of current endosomal disruptive agents, such as high toxicity and low excretion, and are amenable to traditional medicinal chemistry approaches for optimization. In this report, we synthesized three generations of caged surfactants and demonstrated that they can enhance the ability of cationic lipids to deliver mRNA into primary cells. We also show that caged surfactants can deliver siRNA into cells when modified with the RNA-binding dye thiazole orange. We anticipate that the caged surfactants will have numerous applications in pharmaceutical chemistry and drug delivery given their versatility.

Sea salt aerosol (SSA) plays a significant role in the atmosphere through aerosol direct and indirect effects, and in atmospheric chemistry as a source of tropospheric bromine. In situ measurements of coarse-mode SSA particles are limited because of their low concentration and relatively large sizes (dry radius rd > 0.5 μm). With this in mind, a new, low-cost, easily usable method for sampling coarse-mode SSA particles in the marine boundary layer was developed. An SSA particle sampler that uses an impaction method was designed and built using 3D printing and Arduino microcontrollers and sensors. It exposes polycarbonate slides to ambient airflow remotely on a kite-based platform to capture coarse-mode SSA particles. Because it is a smaller version of the Giant Nucleus Impactor (GNI), designed for use on aircraft, it is named the miniature Giant Nucleus Impactor (miniGNI). After sample collection, the same optical microscope methodology utilized by the GNI was used to analyze the wetted salt particles that impacted onto the slides. In this proof-of-concept study, multiple miniGNIs were attached serially to a kite string, allowing for sampling at multiple altitudes simultaneously. The robustness of the results from this new instrument and methodology for sampling at ambient RH (~75%) the SSA particle size distribution with rd > 3.3 μm are compared with a similar study. We find that the SSA particle number concentration decreases weakly with altitude and shows no correlation to instantaneous U10 wind speed along the windward coastline of Oʻahu in the Hawaiian Islands.

Sea spray aerosol (SSA) play a significant role in the local climatology of coastal areas through direct radiative forcing and the indirect aerosol effect. Quantifying the size and concentrations of SSA is essential to understanding their influence in these coastal regions. Current observations of SSA in the surf zone come from coastline station measurements. These stations are often limited to observing only the mass of SSA produced and are unable to differentiate SSA concentrations of varying sizes. NCAR has developed an instrument known as a giant nucleus impactor (GNI) that allows deliquesced salt particles to impact onto polycarbonate slides exposed to a free airstream. These slides are then analyzed in a humidified environment under a microscope providing information about the SSA sizes and concentrations present. By modifying the NCAR GNI, we created a smaller, low-cost method known as a mini-GNI from 3D printing and Arduino microcontrollers. Using this new instrumentation, we attached the mini-GNI to a drone that sampled four locations over the ocean perpendicular to the coastline: the outer reef crest, inner reef crest, lagoon area, and shoreline. While sampling occurred, atmospheric and oceanographic measurements were recorded. This methodology provided us a baseline concentration or “open-ocean” concentration at the outer reef crest. It allowed us to compare how sizes and concentrations changed as the air parcel interacted with the surf zone. As the sampling locations moved closer to the shore, we’ve observed an increase in larger and more concentrated SSA that were contributed by the surf zone. We’ve also found that SSA concentrations have a stronger relationship to wave activity than to wind speed in our coastal environment. The ultimate goal is to quantify how the ocean environment and atmospheric conditions contribute to SSA production in the surf zone.