Zinc-Modified Titanate Nanotubes as Radiosensitizers for Glioblastoma: Enhancing Radiotherapy Efficacy and Monte Carlo Simulations.

Radiotherapy (RT) is the established noninvasive treatment for glioblastoma (GBM), a highly aggressive malignancy. However, its effectiveness in improving patient survival remains limited due to the radioresistant nature of GBM. Metal-based nanostructures have emerged as promising strategies to enhance RT efficacy. Among them, titanate nanotubes (TNTs) have gained significant attention due to their biocompatibility and cost-effectiveness. This study aimed to synthesize zinc-modified TNTs (ZnTNT) from sodium TNTs (NaTNT), in addition to characterizing the formed nanostructures and evaluating their radiosensitization effects in GBM cells (U87 and U251). Hydrothermal synthesis was employed to fabricate the TNTs, which were characterized using various techniques, including transmission electron microscopy (TEM), energy-dispersive spectroscopy, scanning-transmission mode, Fourier-transform infrared spectroscopy, ICP-MS (inductively coupled plasma mass spectrometry), X-ray photoelectron spectroscopy, and zeta potential analysis. Cytotoxicity was evaluated in healthy (Vero) and GBM (U87 and U251) cells by the MTT assay, while the internalization of TNTs was observed through TEM imaging and ICP-MS. The radiosensitivity of ZnTNT and NaTNT combined with 5 Gy was evaluated using clonogenic assays. Monte Carlo simulations using the MCNP6.2 code were performed to determine the deposited dose in the culture medium for RT scenarios involving TNT clusters and cells. The results demonstrated differences in the dose deposition values between the scenarios with and without TNTs. The study revealed that ZnTNT interfered with clonogenic integrity, suggesting its potential as a powerful tool for GBM treatment.

Hyaluronic acid-coated chitosan nanoparticles as carrier for the enzyme/prodrug complex based on horseradish peroxidase/indole-3-acetic acid: Characterization and potential therapeutic for bladder cancer cells.

Hybrid nanoparticles composed of different biopolymers for delivery of enzyme/prodrug systems are of interest for cancer therapy. Hyaluronic acid-coated chitosan nanoparticles (CS/HA NP) were prepared to encapsulate individually an enzyme/pro-drug complex based on horseradish peroxidase (HRP) and indole-3-acetic acid (IAA). CS/HA NP showed size around 158 nm and increase to 170 and 200 nm after IAA and HRP encapsulation, respectively. Nanoparticles showed positive zeta potential values (between +20.36 mV and +24.40 mV) and higher encapsulation efficiencies for both nanoparticles (up to 90 %) were obtained. Electron microscopy indicated the formation of spherical particles with smooth surface characteristic. Physicochemical and thermal characterizations suggest the encapsulation of HRP and IAA. Kinetic parameters for encapsulated HRP were similar to those of the free enzyme. IAA-CS/HA NP showed a bimodal release profile of IAA with a high initial release (72 %) followed by a slow-release pattern. The combination of HRP-CS/HA NP and IAA- CS/HA NP reduced by 88 % the cell viability of human bladder carcinoma cell line (T24) in the concentrations 0.5 mM of pro-drug and 1.2 µg/mL of the enzyme after 24 h.

Chitosan and chitosan/PEG nanoparticles loaded with indole-3-carbinol: Characterization, computational study and potential effect on human bladder cancer cells.

Indole-3-carbinol (I3C) is a plant molecule known to be active against several types of cancer, but some chemical characteristics limit its clinical applications. In order to overcome these limitations, polymeric nanoparticles can be used as carrier systems for targeted delivery of I3C. In this study, chitosan and chitosan/polyethylene glycol nanoparticles (CS NP and CS/PEG NP, respectively) were prepared to encapsulate I3C by ionic gelation method. The polymeric nanoparticles were characterized by Dynamic Scattering Light (DLS), Zeta Potential (ZP), Fourier Transform Infrared (FTIR) spetroscopy, X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Field Emission Gun Scanning Electron Microscopy (FEG-SEM). I3C release testing was performed at an acidic media and the interactions between I3C and chitosan or PEG were evaluated by Density Functional Theory (DFT). Cytotoxicity of nanoparticles in bladder cancer T24 cell line was evaluated by the Methyl-thiazolyl-tetrazolium (MTT) colorimetric assay. The average size of the nanoparticles was observed to be in the range from 133.3 ± 3.7 nm to 180.4 ± 2.7 nm with a relatively homogeneous distribution. Samples had relatively high positive zeta potential values (between +20.3 ± 0.5 mV and + 24.3 ± 0.5 mV). Similar encapsulation efficiencies (about 80%) for both nanoparticles were obtained. Physicochemical and thermal characterizations pointed to the encapsulation of I3c. electron microscopy showed spherical particles with smooth or ragged surface characteristics, depending on the presence of PEG. The mathematical fitting of the release profile demonstrated that I3C-CS NP followed the Higuchi model whereas I3C-CS/PEG NP the Korsmeyer-Peppas model. Chemical differences between the nanoparticles as based on the I3C/CS or I3C/PEG interactions were demonstrate by computational characterization. The assessment of cell viability by the MTT test showed that the presence of both free I3C and I3C-loaded nanoparticles lead to statistically significant reduction in T24 cells viability in the concentrations from 500 to 2000 µM, when comparison to the control group after 24 h of exposure. Thus, CS and CS/PEG nanoparticles present as feasible I3C carrier systems for cancer therapy.