Uptake and Toxicity of Respirable Carbon-Rich Uranium-Bearing Particles: Insights into the Role of Particulates in Uranium Toxicity.

Particulate matter (PM) presents an environmental health risk for communities residing close to uranium (U) mine sites. However, the role of the particulate form of U on its cellular toxicity is still poorly understood. Here, we investigated the cellular uptake and toxicity of C-rich U-bearing particles as a model organic particulate containing uranyl citrate over a range of environmentally relevant concentrations of U (0-445 µM). The cytotoxicity of C-rich U-bearing particles in human epithelial cells (A549) was U-dose-dependent. No cytotoxic effects were detected with soluble U doses. Carbon-rich U-bearing particles with a wide size distribution (<10 µm) presented 2.7 times higher U uptake into cells than the particles with a narrow size distribution (<1 µm) at 100 µM U concentration. TEM-EDS analysis identified the intracellular translocation of clusters of C-rich U-bearing particles. The accumulation of C-rich U-bearing particles induced DNA damage and cytotoxicity as indicated by the increased phosphorylation of the histone H2AX and cell death, respectively. These findings reveal the toxicity of the particulate form of U under environmentally relevant heterogeneous size distributions. Our study opens new avenues for future investigations on the health impacts resulting from environmental exposures to the particulate form of U near mine sites.

Future of Mesoporous Silica Nanoparticles in Nanomedicine: Protocol for Reproducible Synthesis, Characterization, Lipid Coating, and Loading of Therapeutics (Chemotherapeutic, Proteins, siRNA and mRNA).

Owing to their uniform and tunable particle size, pore size, and shape, along with their modular surface chemistry and biocompatibility, mesoporous silica nanoparticles (MSNs) have found extensive applications as nanocarriers to deliver therapeutic, diagnostic and combined "theranostic" cargos to cells and tissues. Although thoroughly investigated, MSN have garnered FDA approval for only one MSN system via oral administration. One possible reason is that there is no recognized, reproducible, and widely adopted MSN synthetic protocol, meaning not all MSNs are created equal in the laboratory nor in the eyes of the FDA. This manuscript provides the sol-gel and MSN research communities a reproducible, fully characterized synthetic protocol to synthesize MSNs and corresponding lipid-coated MSN delivery vehicles with predetermined particle size, pore size, and drug loading and release characteristics. By carefully articulating the step-by-step synthetic procedures and highlighting critical points and troubleshooting, augmented with videos and schematics, this Article will help researchers entering this rapidly expanding field to yield reliable results.

Engineering of monosized lipid-coated mesoporous silica nanoparticles for CRISPR delivery.

CRISPR gene editing technology is strategically foreseen to control diseases by correcting underlying aberrant genetic sequences. In order to overcome drawbacks associated with viral vectors, the establishment of an effective non-viral CRISPR delivery vehicle has become an important goal for nanomaterial scientists. Herein, we introduce a monosized lipid-coated mesoporous silica nanoparticle (LC-MSN) delivery vehicle that enables both loading of CRISPR components [145 µg ribonucleoprotein (RNP) or 40 µg plasmid/mg nanoparticles] and efficient release within cancer cells (70%). The RNP-loaded LC-MSN exhibited 10% gene editing in both in vitro reporter cancer cell lines and in an in vivo Ai9-tdTomato reporter mouse model. The structural and chemical versatility of the mesoporous silica core and lipid coating along with framework dissolution-assisted cargo delivery open new prospects towards safe CRISPR component delivery and enhanced gene editing. STATEMENT OF SIGNIFICANCE: After the discovery of CRISPR gene-correcting technology in bacteria. The translation of this technology to mammalian cells may change the face of cancer therapy within the next years. This was first made possible through the use of viral vectors; however, such systems limit the safe translation of CRISPR into clinics because its difficult preparation and immunogenicity. Therefore, biocompatible non-viral nanoparticulate systems are required to successfully deliver CRISPR into cancer cells. The present study presents the use of biomimetic lipid-coated mesoporous silica nanoparticles showing successful delivery of CRISPR ribonucleoprotein and plasmid into HeLa cervical and A549 lung cancer cells as well as successful gene editing in mice brain.