Receptor Ligand-Free Mesoporous Silica Nanoparticles: A Streamlined Strategy for Targeted Drug Delivery across the Blood-Brain Barrier.

Mesoporous silica nanoparticles (MSNs) represent a promising avenue for targeted brain tumor therapy. However, the blood-brain barrier (BBB) often presents a formidable obstacle to efficient drug delivery. This study introduces a ligand-free PEGylated MSN variant (RMSN25-PEG-TA) with a 25 nm size and a slight positive charge, which exhibits superior BBB penetration. Utilizing two-photon imaging, RMSN25-PEG-TA particles remained in circulation for over 24 h, indicating significant traversal beyond the cerebrovascular realm. Importantly, DOX@RMSN25-PEG-TA, our MSN loaded with doxorubicin (DOX), harnessed the enhanced permeability and retention (EPR) effect to achieve a 6-fold increase in brain accumulation compared to free DOX. In vivo evaluations confirmed the potent inhibition of orthotopic glioma growth by DOX@RMSN25-PEG-TA, extending survival rates in spontaneous brain tumor models by over 28% and offering an improved biosafety profile. Advanced LC-MS/MS investigations unveiled a distinctive protein corona surrounding RMSN25-PEG-TA, suggesting proteins such as apolipoprotein E and albumin could play pivotal roles in enabling its BBB penetration. Our results underscore the potential of ligand-free MSNs in treating brain tumors, which supports the development of future drug-nanoparticle design paradigms.

Three-dimensional hierarchical porous sludge-derived carbon supported on silicon carbide foams as effective and stable Fenton-like catalyst for odorous methyl mercaptan elimination.

The poor reusability of catalysts and secondary pollution are critical issues for sulfur-containing volatile organic compounds (S-VOCs) removal. In this paper, a three-dimensional (3D) hierarchical porous sludge-derived carbon supported on silicon carbide foams (SiC) has been fabricated for deep decomposition of S-VOCs under ambient conditions. The sludge-derived Fenton-like catalyst has been confirmed to be hierarchical 3D porous structure based on detailed characterization by scanning electron microscopy (SEM), X-ray diffraction (XRD), Nitrogen adsorption-desorption measurements and Raman spectroscopy. Significantly, the catalyst after KOH activation (SCFeK-SiC) shows excellent catalytic decomposition of methyl mercaptan (CH3SH) with almost complete CH3SH oxidation into sulfate using hydrogen peroxide as an oxidant under ambient conditions. This catalyst also possesses relative low iron dissolution and excellent cycling performance. The efficient catalytic ability of SCFeK-SiC can be attributed to SiC foam functioned as a stable 3D macroporous skeleton, in which the porous sludge-derived carbon immobilizes the active iron species and promotes the efficient capture of gaseous CH3SH, thus facilitating the decomposition of CH3SH by generating reactive species, specifically ·OH. The reaction mechanism was systematically investigated. Herein, the design of the porous sludge-derived carbonaceous Fenton-like catalyst paves an avenue for efficient VOCs treatment and rational sludge disposal.

Nanoparticle-Cell Interactions: Relevance for Public Health.

Nanoparticles, especially metal oxide nanoparticles, are used in a wide range of commercial and industrial applications that result in direct human contact, such as titanium dioxide nanoparticles in paints, food colorings, and cosmetics, or indirectly through release of nanoparticle-containing materials into the environment. Workers who process nanoparticles for downstream applications are exposed to especially high concentrations of nanoparticles. For physical chemists, nanoparticles present an interesting area of study as the small size of nanoparticles changes the properties from that of the bulk material, leading to novel properties and reactivity. For the public health community, this reduction in particle size means that exposure limits and outcomes that were determined from bulk material properties are not necessarily valid. Informed determination of exposure limits requires a fundamental understanding of how nanoparticles interact with cells. This Feature Article highlights the areas of intersection between physical chemistry and public health in understanding nanoparticle-cell interactions, with a focus on titanium dioxide nanoparticles. It provides an overview of recent research examining the interaction of titanium dioxide nanoparticles with cells in the absence of UV light and provides recommendations for additional nanoparticle-cell research in which physical chemistry expertise could help to inform the public health community.

TiO2 Nanoparticle-Induced Oxidation of the Plasma Membrane: Importance of the Protein Corona.

Titanium dioxide (TiO2) nanoparticles, used as pigments and photocatalysts, are widely present in modern society. Inhalation or ingestion of these nanoparticles can lead to cellular-level interactions. We examined the very first step in this cellular interaction, the effect of TiO2 nanoparticles on the lipids of the plasma membrane. Within 12 h of TiO2 nanoparticle exposure, the lipids of the plasma membrane were oxidized, determined with a malondialdehyde assay. Lipid peroxidation was inhibited by surface passivation of the TiO2 nanoparticles, incubation with an antioxidant (Trolox), and the presence of serum proteins in solution. Subsequent experiments determined that serum proteins adsorbed on the surface of the TiO2 nanoparticles, forming a protein corona, inhibit lipid peroxidation. Super-resolution fluorescence microscopy showed that these serum proteins were clustered on the nanoparticle surface. These protein clusters slow lipid peroxidation, but by 24 h, the level of lipid peroxidation is similar, independent of the protein corona or free serum proteins. Additionally, over 24 h, this corona of proteins was displaced from the nanoparticle surface by free proteins in solution. Overall, these experiments provide the first mechanistic investigation of plasma membrane oxidation by TiO2 nanoparticles, in the absence of UV light and as a function of the protein corona, approximating a physiological environment.

Nanoparticle-induced oxidation of corona proteins initiates an oxidative stress response in cells.

Titanium dioxide nanoparticles (TiO2 NPs), used as pigments and photocatalysts, are ubiquitous in our daily lives. Previous work has observed cellular oxidative stress in response to the UV-excitation of photocatalytic TiO2 NPs. In comparison, most human exposure to TiO2 NPs takes place in the dark, in the lung following inhalation or in the gut following consumption of TiO2 NP food pigment. Our spectroscopic characterization shows that both photocatalytic and food grade TiO2 NPs, in the dark, generate low levels of reactive oxygen species (ROS), specifically hydroxyl radicals and superoxides. These ROS oxidize serum proteins that form a corona of proteins on the NP surface. This protein layer is the interface between the NP and the cell. An oxidized protein corona triggers an oxidative stress response, detected with PCR and western blotting. Surface modification of TiO2 NPs to increase or decrease surface defects correlates with ROS generation and oxidative stress, suggesting that NP surface defects, likely oxygen vacancies, are the underlying cause of TiO2 NP-induced oxidative stress.