Multimodal neuro-nanotechnology: Challenging the existing paradigm in glioblastoma therapy.

Integrating multimodal neuro- and nanotechnology-enabled precision immunotherapies with extant systemic immunotherapies may finally provide a significant breakthrough for combatting glioblastoma (GBM). The potency of this approach lies in its ability to train the immune system to efficiently identify and eradicate cancer cells, thereby creating anti-tumor immune memory while minimizing multi-mechanistic immune suppression. A critical aspect of these therapies is the controlled, spatiotemporal delivery of structurally defined nanotherapeutics into the GBM tumor microenvironment (TME). Architectures such as spherical nucleic acids or poly(beta-amino ester)/dendrimer-based nanoparticles have shown promising results in preclinical models due to their multivalency and abilities to activate antigen-presenting cells and prime antigen-specific T cells. These nanostructures also permit systematic variation to optimize their distribution, TME accumulation, cellular uptake, and overall immunostimulatory effects. Delving deeper into the relationships between nanotherapeutic structures and their performance will accelerate nano-drug development and pave the way for the rapid clinical translation of advanced nanomedicines. In addition, the efficacy of nanotechnology-based immunotherapies may be enhanced when integrated with emerging precision surgical techniques, such as laser interstitial thermal therapy, and when combined with systemic immunotherapies, particularly inhibitors of immune-mediated checkpoints and immunosuppressive adenosine signaling. In this perspective, we highlight the potential of emerging treatment modalities, combining advances in biomedical engineering and neurotechnology development with existing immunotherapies to overcome treatment resistance and transform the management of GBM. We conclude with a call to action for researchers to leverage these technologies and accelerate their translation into the clinic.

Molecular Thin Films Enable the Synthesis and Screening of Nanoparticle Megalibraries Containing Millions of Catalysts.

Megalibraries are centimeter-scale chips containing millions of materials synthesized in parallel using scanning probe lithography. As such, they stand to accelerate how materials are discovered for applications spanning catalysis, optics, and more. However, a long-standing challenge is the availability of substrates compatible with megalibrary synthesis, which limits the structural and functional design space that can be explored. To address this challenge, thermally removable polystyrene films were developed as universal substrate coatings that decouple lithography-enabled nanoparticle synthesis from the underlying substrate chemistry, thus providing consistent lithography parameters on diverse substrates. Multi-spray inking of the scanning probe arrays with polymer solutions containing metal salts allows patterning of >56 million nanoreactors designed to vary in composition and size. These are subsequently converted to inorganic nanoparticles via reductive thermal annealing, which also removes the polystyrene to deposit the megalibrary. Megalibraries with mono-, bi-, and trimetallic materials were synthesized, and nanoparticle size was controlled between 5 and 35 nm by modulating the lithography speed. Importantly, the polystyrene coating can be used on conventional substrates like Si/SiOx, as well as substrates typically more difficult to pattern on, such as glassy carbon, diamond, TiO2, BN, W, or SiC. Finally, high-throughput materials discovery is performed in the context of photocatalytic degradation of organic pollutants using Au-Pd-Cu nanoparticle megalibraries on TiO2 substrates with 2,250,000 unique composition/size combinations. The megalibrary was screened within 1 h by developing fluorescent thin-film coatings on top of the megalibrary as proxies for catalytic turnover, revealing Au0.53Pd0.38Cu0.09-TiO2 as the most active photocatalyst composition.

Colloidal stabilization of hydrophobic InSe 2D nanosheets in a model environmental aqueous solution and their impact on Shewanella oneidensis MR-1.

Semiconductor InSe 2D nanomaterials have emerged as potential photoresponsive materials for broadly distributed photodetectors and wearable electronics technologies due to their high photoresponsivity and thermal stability. This paper addresses an environmental concern about the fate of InSe 2D nanosheets when disposed and released into the environment after use. Semiconducting materials are potentially reactive and often form environmentally damaging species, for example reactive oxygen and nitrogen species, when degraded. InSe nanosheets are prepared using a semi bottom-up approach which involves a reaction between indium and selenium precursors at elevated temperature in an oxygen-free environment to prevent oxidation. InSe nanosheets are formed as a stable intermediate with micrometer-sized lateral dimensions and a few monolayer thickness. The InSe 2D nanosheets are obtained when the reaction is stopped after 30 minutes by cooling. Keeping the reaction at elevated temperature for a longer period, for example 60 minutes leads to the formation of InSe 3D nanoparticles of about 5 nm in diameter, a thermodynamically more stable form of InSe. The paper focuses on the colloidal stabilization of InSe nanosheets in an aqueous solution that contains epigallocatechin gallate (EGCG), a natural organic matter (NOM) simulant. We show that EGCG coats the surface of the hydrophobic, water-insoluble InSe nanosheets via physisorption. The formed EGCG-coated InSe nanosheets are colloidally stable in aqueous solution. While unmodified semiconducting InSe nanosheets could produce reactive oxygen species (ROS) when illuminated, our study shows low levels of ROS generation by EGCG-coated InSe nanosheets under ambient light, which might be attributed to ROS quenching by EGCG. Growth-based viability (GBV) assays show that the colloidally stable EGCG-coated InSe nanosheets adversely impact the bacterial growth of Shewanella oneidensis MR-1, an environmentally relevant Gram-negative bacterium in aqueous media. The impact on bacterial growth is driven by the EGCG coating of the nanosheets. In addition, live/dead assays show insignificant membrane damage of the Shewanella oneidensis MR-1 cells by InSe nanosheets, suggesting a weak association of EGCG-coated nanosheets with the cells. It is likely that the adverse impact of EGCG-coated nanosheets on bacterial growth is the result of increasing local concentration of EGCG either when adsorbed on the nanosheets when the nanosheets interact with the cells, or when desorbed from the EGCG-coated nanosheets to interact with the bacterial cells.

Influence of CuO Nanoparticle Aspect Ratio and Surface Charge on Disease Suppression in Tomato (Solanum lycopersicum).

Nanoparticles (NPs) have been shown to deliver micronutrients to plants to improve health, increase biomass, and suppress disease. Nanoscale properties such as morphology, size, composition, and surface chemistry have all been shown to impact nanomaterial interactions with plant systems. An organic-ligand-free synthesis method was used to prepare positively charged copper oxide (CuO) nanospikes, negatively charged CuO nanospikes, and negatively charged CuO nanosheets with exposed (001) crystal faces. X-ray photoelectron spectroscopy measurements show that the negative charge correlates to increased surface concentration of O on the NP surface, whereas relatively higher Cu concentrations are observed on the positively charged surfaces. The NPs were then used to treat tomato (Solanum lycopersicum) grown in soil infested with Fusarium oxysporum f. sp. lycopersici under greenhouse conditions. The negatively charged CuO significantly reduced disease progression and increased biomass, while the positively charged NPs and a CuSO4 salt control had little impact on the plants. Self-assembled monolayers were used to mimic the leaf surface to understand the intermolecular interactions between the NPs and the plant leaf; the data demonstrate that NP electrostatics and hydrogen-bonding interactions play an important role in adsorption onto leaf surfaces. These findings have important implications for the tunable design of materials as a strategy for the use of nano-enabled agriculture to increase food production.

Expression Patterns of Energy-Related Genes in Single Cells Uncover Key Isoforms and Enzymes That Gain Priority Under Nanoparticle-Induced Stress.

Cellular responses to nanoparticles (NPs) have been largely studied in cell populations, providing averaged values that often misrepresent the true molecular processes that occur in the individual cell. To understand how a cell redistributes limited molecular resources to achieve optimal response and survival requires single-cell analysis. Here we applied multiplex single molecule-based fluorescence in situ hybridization (fliFISH) to quantify the expression of 10 genes simultaneously in individual intact cells, including glycolysis and glucose transporter genes, which are critical for restoring and maintaining energy balance. We focused on individual gill epithelial cell responses to lithium cobalt oxide (LCO) NPs, which are actively pursued as cathode materials in lithium-ion batteries, raising concerns about their impact on the environment and human health. We found large variabilities in the expression levels of all genes between neighboring cells under the same exposure conditions, from only a few transcripts to over 100 copies in individual cells. Gene expression ratios among the 10 genes in each cell uncovered shifts in favor of genes that play key roles in restoring and maintaining energy balance. Among these genes are isoforms that can secure and increase glycolysis rates more efficiently, as well as genes with multiple cellular functions, in addition to glycolysis, including DNA repair, regulation of gene expression, cell cycle progression, and proliferation. Our study uncovered prioritization of gene expression in individual cells for restoring energy balance under LCO NP exposures. Broadly, our study gained insight into single-cell strategies for redistributing limited resources to achieve optimal response and survival under stress.