Search Results (52)

Glioblastoma (GBM) is an aggressive and common form of central nervous system primary malignant tumor in adults. GBM accounts for about half of all gliomas. Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12–15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance. Recurrence is nearly universal, underscoring the need for novel therapies. Oncolytic virotherapy demonstrates a promising strategy that combines direct tumor cell lysis with immune activation. Tumor-selective viruses replicate within malignant cells, induce cell death, and release tumor antigens, thereby reshaping the immunosuppressive microenvironment. Several viral backbones have advanced to clinical testing, including adenovirus (DNX-2401), herpes simplex virus (G47Δ, G207), poliovirus (PVS-RIPO), measles virus (MV-CEA), reovirus (pelareorep), vaccinia virus (Pexa-Vec), and vesicular stomatitis virus (VSV-GP). The approval of G47Δ in Japan for malignant glioma marks a milestone, with early trials demonstrating safety and signals of durable benefit, particularly in combination regimens. Current research emphasizes engineering viral genomes to enhance selectivity, immune stimulation, and resistance to clearance, while exploring synergistic combinations with radiotherapy, chemotherapy, immune checkpoint inhibitors, and tumor-treating fields. Advances in delivery, such as convection-enhanced infusion and blood–brain barrier modulation, are also under investigation. Despite obstacles, oncolytic virotherapy holds significant potential within multimodal GBM strategies. Full article

Our study investigates how non-spherical bubble shapes influence gas–liquid mass transfer across the bubble interface. An analytical shape descriptor, namely Superformula, is used to parametrically define the bubble interface, enabling efficient CFD simulations over a range of Reynolds ($Re$) and Eötvös ($Eo$) numbers. By prescribing the bubble geometry analytically, we avoid expensive interface-capturing simulations and directly compute the concentration field without transient boundary shape pre-equilibration. The represented approach is computationally efficient and captures the impact of bubble shape and flow parameters on the dissolved gas concentration gradients in the surrounding liquid. Results show that bubble deformation alters the distribution of dissolved gas around the bubble and the overall mass transfer rate, with higher $Re$ enhancing convective transport and higher $Eo$ (more deformed bubbles), leading to anisotropic concentration boundary layers. The developed framework not only advances a fundamental understanding of bubble-driven mass transfer mechanisms but also directly addresses industrial needs, particularly in optimizing oxygen delivery within bioreactors contour and similar aerated processes. The proposed efficient modeling strategy provides a basis for developing fast surrogate tools in hybrid modeling frameworks, where high-fidelity CFD insights are incorporated into larger-scale multiphase process simulations. Full article

Tumors of the central nervous system (CNS) represent a unique therapeutic challenge due to the complexity of the CNS and the protective role of the blood–brain barrier (BBB). All gliomas are of glial origin, account for the majority of CNS tumors, and are classified by the World Health Organization into four grades based on malignancy. High-grade gliomas, such as glioblastoma multiforme (GBM), exhibit aggressive growth, resistance to treatment, and poor prognosis. Despite significant advancements in cancer therapy, effective drug delivery to CNS tumors remains limited due to pharmacokinetic barriers, especially the BBB, and tumor-related resistance mechanisms. This review highlights the biological characteristics of gliomas and emphasizes the current challenges in achieving effective CNS tumor treatment. Full article

Rapid mixing is widely prevalent in the field of microfluidics, encompassing applications such as biomedical diagnostics, drug delivery, chemical synthesis, and enzyme reactions. Mixing efficiency profoundly impacts the overall performance of these devices. However, at the micro-scale, the flow typically presents as laminar flow due to low Reynolds numbers, rendering rapid mixing challenging. Leveraging the vortices within a droplet of the Taylor flow and inducing chaotic convection within the droplet through serpentine channels can significantly enhance mixing efficiency. Based on this premise, we have developed a droplet micromixer that integrates the T-shaped channels required for generating Taylor flow and the serpentine channels required for inducing chaotic convection within the droplet. We determined the range of inlet liquid flow rate and gas pressure required to generate Taylor flow and conducted experimental investigations to examine the influence of the inlet conditions on droplet length, total flow rate, and mixing efficiency. Under conditions where channel dimensions and liquid flow rates are identical, Taylor flow achieves a nine-fold improvement in mixing efficiency compared to single-phase flow. At low Reynolds number (0.57 ≤ Re ≤ 1.05), the chip can achieve a 95% mixing efficiency within a 2 cm distance in just 0.5–0.8 s. The mixer proposed in this study offers the advantages of simplicity in manufacturing and ease of integration. It can be readily integrated into Lab-on-a-Chip devices to perform critical functions, including microfluidic switches, formation of nanocomposites, synthesis of oxides and adducts, velocity measurement, and supercritical fluid fractionation. Full article

Hydrogels have become indispensable in biomedical research and regenerative therapies due to their high water content, tissue-like mechanics, and tunable biochemical properties. However, their behavior under altered gravitational conditions—particularly simulated microgravity (SMG)—presents a frontier of challenges and opportunities that remain underexplored. This comprehensive review provides a detailed comparative analysis of hydrogel performance in normal gravity versus SMG environments, focusing on the structural, physicochemical, and thermodynamic parameters that govern their functionality. We critically examine how microgravity influences polymer network formation, fluid dynamics, swelling behavior, mechanical stability, and degradation kinetics. SMG disrupts convection, sedimentation, and phase separation, often leading to inhomogeneous crosslinking and altered diffusion profiles. These changes can compromise hydrogel uniformity, anisotropy, and responsiveness, which are essential for biomedical applications such as drug delivery, tissue regeneration, and biosensing. To address these limitations, we propose a thermodynamic framework that integrates osmotic pressure regulation, entropy-driven swelling, and pressure–temperature control to enhance hydrogel stability and functionality in low-gravity environments. The integration of predictive modeling approaches—including finite element simulations, phase-field models, and swelling kinetics—provides a robust pathway to design space-adapted hydrogel systems. The review also outlines future directions for optimizing hydrogel platforms in extraterrestrial settings, advocating for synergistic advances in material science, biophysics, and space health. These insights offer a strategic foundation for the rational development of next-generation hydrogel technologies tailored for long-duration space missions and planetary biomedical infrastructure. Full article

A very aggressive and deadly brain cancer, glioblastoma multiforme (GBM) poses formidable obstacles to effective therapy. Despite advancements in conventional therapies like surgery, chemotherapy, and radiation therapy, the prognosis for GBM patients remains poor, with limited survival outcomes. Nanotechnology is gaining popularity as a promising platform for managing GBM, offering targeted drug delivery, improved therapeutic efficacy, and reduced systemic toxicity. This review offers a comprehensive analysis of the current therapeutic approach for GBM using nanotechnology-based interventions. This study explored various nanocarrier (NC) systems like polymeric nanoparticles, liposomes, dendrimers, polymeric micelles, and mesoporous silica nanoparticles for improved precision as well as efficacy in encapsulating and delivering therapeutic agents to GBM tumors. Methods for improving drug delivery into GBM cells are described in this study, including novel delivery modalities such as convection-enhanced delivery, intranasal administration, magnetic hyperthermia, peptide-guided nanoparticles, and immune liposomes. It also explores the influence of diabetes and obesity on GBM prognosis and survival rates, suggesting that managing glucose levels and using metformin may improve patient outcomes. The discussion focuses on the advancements in nanotechnology-enabled GBM therapy, highlighting the challenges and opportunities in implementing these promising technologies in clinical practice. The study highlights the potential of nanotechnology and metabolic modulation in transforming GBM treatment strategies. To further understand how these factors impact GBM patients and develop innovative nanotechnology-based treatments for GBM and diabetes mellitus, more study is necessary. Full article

This work presents advancements in a rotating glow-to-arc plasma reactor, designed for stable gas conversion of robust molecules like CO₂, N₂, and CH₄. Plasma-based systems play a critical role in Power-to-X research, offering electrified, sustainable pathways for industrial gas conversion. Here, we scaled the reactor’s power from 200 W to 1.2 kW in a CO₂ plasma, which introduced instability due to uplift forces and arc behavior. These were mitigated by integrating silicon carbide (SiC) ceramic foam as a mechanical restriction, significantly enhancing stability by reducing arc movement, confining convection, and balancing volumetric flow within the arc. Using high-speed camera analysis and in situ electronic frequency measurements, we identified dominant frequencies tied to operational parameters, supporting potential in operando monitoring and control. Arc-rotation frequencies from 5 to 50 Hz and higher frequencies (500 to 2700 Hz) related to arc chattering reveal the system’s dynamic response to power and flow changes. Furthermore, refining the specific energy input ($SEI$) to account for plasma residence time allowed for a more precise calculation of effective $SEI$, optimizing energy delivery to target molecules. Our findings underscore the reactor’s promise for scalable, efficient gas conversion in sustainable energy applications. Full article

A theoretical simulation is performed to evaluate how microcracks affect the flow resistance in tumors during the convection-enhanced delivery (CED) of nanofluids. Both Darcy’s law and the theory of poroelasticity are used to understand fluid transport with or without microcrack introduction and/or enlargement. The results demonstrate significantly altered pressure and velocity fields in a spherical tumor with a radius of 10 mm due to the presence of a microcrack with a radius of 0.05 mm and length of 3 mm. The non-uniform fluid pressure field enlarges the original cylindrical microcrack to a frustum, with the crack volume more than doubled. Due to the larger permeability and porosity in the microcrack, flow in the tumor is much easier. One finds that the flow resistance with the enlarged microcrack is reduced by 14% from the control without a microcrack. Parametric studies are conducted to show that larger crack radii, longer crack lengths and higher infusing pressures result in further resistance reductions. The largest resistance reduction occurs when the infusing pressure is 4 × 10⁵ Pa and the microcrack is 9 mm long, up to 18% from the control. We conclude that introducing a microcrack is an effective way to facilitate nanofluid delivery in porous tumors using CED. Full article

Glioblastoma remains a devastating disease with a bleak prognosis despite continued research and numerous clinical trials. Convection-enhanced delivery offers researchers and clinicians a platform to bypass the blood–brain barrier and administer drugs directly to the brain parenchyma. While not without significant technological challenges, convection-enhanced delivery theoretically allows for a wide range of therapeutic agents to be delivered to the tumoral space while preventing systemic toxicities. This article provides a comprehensive review of the antitumor agents studied in clinical trials of convection-enhanced delivery to treat adult high-grade gliomas. Agents are grouped by classes, and preclinical evidence for these agents is summarized, as is a brief description of their mechanism of action. The strengths and weaknesses of each clinical trial are also outlined. By doing so, the difficulty of untangling the efficacy of a drug from the technological challenges of convection-enhanced delivery is highlighted. Finally, this article provides a focused review of some therapeutics that might stand to benefit from future clinical trials for glioblastoma using convection-enhanced delivery. Full article

Knowing how to accumulate boron into the tumor cells is a crucial aspect of boron neutron capture therapy (BNCT), which can be targeted at the cellular level, and the development of novel boron agents other than BPA, which is used in clinical practice, is urgently needed [...] Full article

Glioblastoma, a grade 4 glioma as per the World Health Organization, poses a challenge in adult primary brain tumor management despite advanced surgical techniques and multimodal therapies. This review delves into the potential of targeting epidermal growth factor receptor (EGFR) with small-molecule inhibitors and antibodies as a treatment strategy. EGFR, a mutationally active receptor tyrosine kinase in over 50% of glioblastoma cases, features variants like EGFRvIII, EGFRvII and missense mutations, necessitating a deep understanding of their structures and signaling pathways. Although EGFR inhibitors have demonstrated efficacy in other cancers, their application in glioblastoma is hindered by blood–brain barrier penetration and intrinsic resistance. The evolving realm of nanodrugs and convection-enhanced delivery offers promise in ensuring precise drug delivery to the brain. Critical to success is the identification of glioblastoma patient populations that benefit from EGFR inhibitors. Tools like radiolabeled anti-EGFR antibody 806i facilitate the visualization of EGFR conformations, aiding in tailored treatment selection. Recognizing the synergistic potential of combination therapies with downstream targets like mTOR, PI3k, and HDACs is pivotal for enhancing EGFR inhibitor efficacy. In conclusion, the era of precision oncology holds promise for targeting EGFR in glioblastoma, contingent on tailored treatments, effective blood–brain barrier navigation, and the exploration of synergistic therapies. Full article

The blood–brain barrier (BBB) poses a significant challenge to drug delivery for brain tumors, with most chemotherapeutics having limited permeability into non-malignant brain tissue and only restricted access to primary and metastatic brain cancers. Consequently, due to the drug’s inability to effectively penetrate the BBB, outcomes following brain chemotherapy continue to be suboptimal. Several methods to open the BBB and obtain higher drug concentrations in tumors have been proposed, with the selection of the optimal method depending on the size of the targeted tumor volume, the chosen therapeutic agent, and individual patient characteristics. Herein, we aim to comprehensively describe osmotic disruption with intra-arterial drug administration, intrathecal/intraventricular administration, laser interstitial thermal therapy, convection-enhanced delivery, and ultrasound methods, including high-intensity focused and low-intensity ultrasound as well as tumor-treating fields. We explain the scientific concept behind each method, preclinical/clinical research, advantages and disadvantages, indications, and potential avenues for improvement. Given that each method has its limitations, it is unlikely that the future of BBB disruption will rely on a single method but rather on a synergistic effect of a combined approach. Disruption of the BBB with osmotic infusion or high-intensity focused ultrasound, followed by the intra-arterial delivery of drugs, is a promising approach. Real-time monitoring of drug delivery will be necessary for optimal results. Full article

Nuclear fission reactions can release massive amounts of energy accompanied by neutrons and γ photons, which create a mixed radiation field and enable a series of reactions in nuclear reactors. This study demonstrates a one-pot/one-step approach to synthesizing radioactive gold nanoparticles (RGNP) without using radioactive precursors and reducing agents. Trivalent gold ions are reduced into gold nanoparticles (8.6–146 nm), and a particular portion of ¹⁹⁷Au atoms is simultaneously converted to ¹⁹⁸Au atoms, rendering the nanoparticles radioactive. We suggest that harnessing nuclear energy to gold nanoparticles is feasible in the interests of advancing nanotechnology for cancer therapy. A combination of RGNP applied through convection-enhanced delivery (CED) and temozolomide (TMZ) through oral administration demonstrates the synergistic effect in treating glioblastoma-bearing mice. The mean survival for RGNP/TMZ treatment was 68.9 ± 9.7 days compared to that for standalone RGNP (38.4 ± 2.2 days) or TMZ (42.8 ± 2.5 days) therapies. Based on the verification of bioluminescence images, positron emission tomography, and immunohistochemistry inspection, the combination treatment can inhibit the proliferation of glioblastoma, highlighting the niche of concurrent chemoradiotherapy (CCRT) attributed to RGNP and TMZ. Full article

This study describes the synthesis, radiofluorination and purification of an anionic amphiphilic teroligomer developed as a stabilizer for siRNA-loaded calcium phosphate nanoparticles (CaP-NPs). As the stabilizing amphiphile accumulates on nanoparticle surfaces, the fluorine-18-labeled polymer should enable to track the distribution of the CaP-NPs in brain tumors by positron emission tomography after application by convection-enhanced delivery. At first, an unmodified teroligomer was synthesized with a number average molecular weight of 4550 ± 20 Da by free radical polymerization of a defined composition of methoxy-PEG-monomethacrylate, tetradecyl acrylate and maleic anhydride. Subsequent derivatization of anhydrides with azido-TEG-amine provided an azido-functionalized polymer precursor (o14PEGMA-N₃) for radiofluorination. The ¹⁸F-labeling was accomplished through the copper-catalyzed cycloaddition of o14PEGMA-N₃ with diethylene glycol–alkyne-substituted heteroaromatic prosthetic group [¹⁸F]2, which was synthesized with a radiochemical yield (RCY) of about 38% within 60 min using a radiosynthesis module. The ¹⁸F-labeled polymer [¹⁸F]fluoro-o14PEGMA was obtained after a short reaction time of 2–3 min by using CuSO₄/sodium ascorbate at 90 °C. Purification was performed by solid-phase extraction on an anion-exchange cartridge followed by size-exclusion chromatography to obtain [¹⁸F]fluoro-o14PEGMA with a high radiochemical purity and an RCY of about 15%. Full article

In recent years, steerable needles have attracted significant interest in relation to minimally invasive surgery (MIS). Specifically, the flexible, programmable bevel-tip needle (PBN) concept was successfully demonstrated in vivo in an evaluation of the feasibility of convection-enhanced delivery (CED) for chemotherapeutics within the ovine model with a 2.5 mm PBN prototype. However, further size reductions are necessary for other diagnostic and therapeutic procedures and drug delivery operations involving deep-seated tissue structures. Since PBNs have a complex cross-section geometry, standard production methods, such as extrusion, fail, as the outer diameter is reduced further. This paper presents our first attempt to demonstrate a new manufacturing method for PBNs that employs thermal drawing technology. Experimental characterisation tests were performed for the 2.5 mm PBN and the new 1.3 mm thermally drawn (TD) PBN prototype described here. The results show that thermal drawing presents a significant advantage in miniaturising complex needle structures. However, the steering behaviour was affected due to the choice of material in this first attempt, a limitation which will be addressed in future work. Full article