No abstract

Infusion reactions (IRs) create a translational hurdle for many novel therapeutics, including those utilizing nanotechnology. Nucleic acid nanoparticles (NANPs) are a novel class of therapeutics prepared by rational design of relatively short oligonucleotides to self-assemble into various programmable geometric shapes. While cytokine storm, a common type of IR, has halted clinical development of several therapeutic oligonucleotides, NANP technologies hold tremendous potential to bring these reactions under control by tuning the particle’s physicochemical properties to the desired type and magnitude of the immune response. Recently, we reported the very first comprehensive study of the structure–activity relationship between NANPs’ shape, size, composition, and their immunorecognition in human cells, and identified the phagolysosomal pathway as the major route for the NANPs’ uptake and subsequent immunostimulation. Here, we explore the molecular mechanism of NANPs’ recognition by primary immune cells, and particularly the contributing role of the Toll-like receptors. Our current study expands the understanding of the immune recognition of engineered nucleic acid-based therapeutics and contributes to the improvement of the nanomedicine safety profile.

It is well-known that Ag–Au bimetallic nanoplates have attracted significant research interest due to their unique plasmonic properties and surface-enhanced Raman scattering (SERS).

The growing interest in engineered tumor models prompted us to devise a method for the non-invasive assessment of such models. Here, we report on bioluminescence imaging (BLI) for the assessment of engineered tumor models in the fertilized chicken egg, i.e, chick chorioallantoic membrane (CAM) assay. One prostate cancer (PC-3) and two osteosarcoma (MG63 and HOS) cell lines were modified with luciferase reporter genes. To create engineered tumors, these cell lines were seeded either onto basement membrane extract (BME) or gelfoam scaffolds, and subsequently grafted in vivo onto the CAM. BLI enabled non-invasive, specific detection of the engineered tumors on the CAM in the living chicken embryo. Further, BLI permitted daily, quantitative monitoring of the engineered tumors over the course of up to 7 days. Data showed that an extracellular matrix (ECM) composed of BME supported growth of reporter gene marked PC-3 tumors but did not support MG63 or HOS tumor growth. However, MG63 tumors engineered on the collagen-based gelfoam ECM showed a temporal proliferation burst in MG63 tumors. Together, the data demonstrated imaging of engineered human cancer models in living chicken embryos. The combination of CAM assay and BLI holds significant potential for the examination of a broad range of engineered tumor models.

Nitrogen-doped TiO2 nanotube arrays (N-TNAs) were successfully fabricated by a simple thermal annealing process in ambient N2 gas at 450 °C for 3 h. TNAs with modified morphologies were prepared by a two-step anodization using an aqueous NH4F/ethylene glycol solution. The N-doping concentration (0–9.47 at %) can be varied by controlling N2 gas flow rates between 0 and 500 cc/min during the annealing process. Photocatalytic performance of as-prepared TNAs and N-TNAs was studied by monitoring the methylene blue degradation under visible light (λ ≥ 400 nm) illumination at 120 mW·cm−2. N-TNAs exhibited appreciably enhanced photocatalytic activity as compared to TNAs. The reaction rate constant for N-TNAs (9.47 at % N) reached 0.26 h−1, which was a 125% improvement over that of TNAs (0.115 h−1). The significant enhanced photocatalytic activity of N-TNAs over TNAs is attributed to the synergistic effects of (1) a reduced band gap associated with the introduction of N-doping states to serve as carrier reservoir, and (2) a reduced electron‒hole recombination rate.