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.

New quercetin-coated titanate nanotubes and their radiosensitization effect on human bladder cancer.

Interest in nanostructures such as titanate nanotubes (TNT) has grown notably in recent years due to their biocompatibility and economic viability, making them promising for application in the biomedical field. Quercetin (Qc) has shown great potential as a chemopreventive agent and has been widely studied for the treatment of diseases such as bladder cancer. Motivated by the possibilities of developing a new hybrid nanostructure with potential in biomedical applications, this study aimed to investigate the incorporation of quercetin in sodium (NaTNT) and zinc (ZnTNT) titanate nanotubes, and characterize the nanostructures formed. Qc release testing was also performed and cytotoxicity in Vero and T24 cell lines evaluated by the MTT assay. The effect of TNTs on T24 bladder cancer cell radiosensitivity was also assessed, using cell proliferation and a clonogenic assay. The TNT nanostructures were synthesized and characterized by FESEM, EDS, TEM, FTIR, XRD and TGA. The results showed that the nanostructures have a tubular structure and that the exchange of Na+ ions for Zn2+ and incorporation of quercetin did not alter this morphology. In addition, interaction between Zn and Qc increased the thermal stability of the nanostructures. The release test showed that maximum Qc delivery occurred after 24 h and the presence of Zn controlled its release. Biological assays indicated that the NaTNTQc and ZnTNTQc nanostructures decreased the viability of T24 cells after 48 h at high concentrations. Furthermore, the clonogenic assay showed that NaTNT, NaTNTQc, ZnTNT and ZnTNTQc combined with 5 Gy reduced the formation of polyclonal colonies of T24 cells after 48 h. The results suggest that the nanostructures synthesized in this study interfere in cell proliferation and can therefore be a powerful tool in the treatment of bladder cancer.