Electrospray Functionalization of Titanium Dioxide Nanoparticles with Transferrin for Cerenkov Radiation Induced Cancer Therapy (original) (raw)
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Interrogation of EGFR-Targeted Uptake of TiO[sub 2] Nanoconjugates by X-ray Fluorescence Microscopy
AIP Conference Proceedings, 2011
We are developing TiO 2 nanoconjugates that can be used as therapeutic and diagnostic agents. Nanoscale TiO 2 can be surface conjugated with various molecules and has the unique ability to induce the production of reactive oxygen species after radiation activation. One way to improve the potential clinical usefulness of TiO 2 nanoparticles is to control their delivery to malignant cells by targeting them to cancer cell specific antigens. Epidermal Growth Factor Receptor is one potential target that is enriched in epithelial cancers and is rapidly internalized after ligand binding. Hence, we have synthesized TiO 2 nanoparticles and functionalized them with a short EGFR binding peptide to create EGFR-targeted NCs. X-ray Fluorescence Microscopy was used to image nanoconjugates within EGFR positive HeLa cells. Further labeling of fixed cells with antibodies against EGFR and Protein A nanogold showed that TiO 2 nanoconjugates can colocalize with receptors at the cell's plasma membrane. Interestingly, with increased incubation times, EGFR targeted nanoconjugates could also be found colocalized with EGFR within the cell nucleus. This suggests that EGFR-targeted nanoconjugates can bind the receptor at the cell membrane, which leads to the internalization of NC-receptor complexes and the subsequent transport of nanoconjugates into the nucleus.
EGF Conjugation Improves Safety and Uptake Efficacy of Titanium Dioxide Nanoparticles
Molecules
Titanium dioxide nanoparticles (TiO2 NPs) have a strong potential for cancer therapeutic and bioimaging applications such as photodynamic therapy (PDT) and photodynamic diagnosis (PDD). Our previous results have shown that TiO2 NPs have a low cellular uptake and can induce cell proliferation. This suggests that TiO2 NPs could increase the risk of tumor overgrowth while being used for PDD and PDT. To solve this problem, we constructed epidermal growth factor-ligated polyethylene glycol-coated TiO2 NPs (EGF-TiO2 PEG NPs). In this work, we studied the effect of EGF conjugation on the cellular uptake of TiO2 PEG NPs. Then, we investigated the effect of both non-conjugated and EGF-TiO2 PEG NPs on the A431 epidermal cancer cell line, proliferation and growth via the investigation of EGFR localization and expression. Our results indicated that TiO2 PEG NPs induced EGFRs aggregation on the A431 cells surface and induced cell proliferation. In addition, EGF-TiO2 PEG NPs induced the internali...
Coupling of photodynamic therapy (PDT) with chemotherapy is an emerging treatment modality because of its ability to improve the antitumor effect and reduce the toxicity of the anticancer agents. Metallic NPs, silica NPs and carbon nanotubes have become rising stars as drug carriers for both photosensitizers and chemotherapeutic agents. But to date there are only a few reports using the aforesaid NPs as a platform for PDT combined with chemotherapy. Hence, we have developed a targeted metallic single nanoparticle system for the amalgamation of PDT with chemotherapy. The NPs for combination therapy have been constructed using two main ingredients: folic acid decorated TiO2 NPs and coumarin chromophore. The newly synthesized coumarin chromophore performed three important roles: (i) being a fluorophore for cell imaging, (ii) photosensitizer for PDT and (iii) a phototrigger for regulated anticancer drug release. Furthermore, folic acid decorated TiO2 NPs help with internalization of the drug to inside the cancer cells. In vitro biological studies reveal that this targeted combination treatment results in an enhanced tumor accumulation of TiO2 nanoparticles, significant inhibition of tumor cell proliferation and increased induction of apoptosis. Such metallic photoresponsive NPs that are benign to the physiological system, permeate easily into cells and exhibit high therapeutic efficacy, will have significant prospects for use against drug-resistant tumors.
Journal of Photochemistry and Photobiology A: Chemistry, 2010
The photo-induced bioactivity of titanium dioxide was investigated in terms of determining the conditions for photocatalytic treatment of cancer cells and also exploring the molecular mechanisms involved in this process. Cultured MCF-7 and MDA-MB-468 breast cancer epithelial cells were irradiated, using UV-A light (wavelength 350 nm) for 20 min, in the presence of nanostructured titania aqueous dispersions prepared using the sol-gel technique. Detailed characterization of the titania sols confirmed the presence of the photocatalyst in the form of anatase nanoparticles. Two different techniques were employed to examine the effects on cell cycle and the viability of the treated culture: propidium iodide (PI) flow cytometric (FACScan) assays permitted the identification of treatment effects on the cell cycle and cell viability analysis (MTT assays) allowed the definition of the precise percentage of cells that are still alive and functionable, after the treatment. A selective action of both TiO 2 nanoparticles and photocatalytically activated titania was observed on the highly malignant MDA-MB-468 cells. Upon irradiation, these cells were induced to undergo apoptotic cell death, compared to the MCF-7 cells which were still unimpaired. This was profoundly revealed via Western blot analysis. The molecular mechanism of apoptosis is associated at least in part with increase of caspase-3-mediated poly(ADP-ribose) polymerase (PARP) cleavage.
Nanomedicine: Photo-activated nanostructured titanium dioxide, as a promising anticancer agent
Pharmacology & Therapeutics
The multivariate condition of cancer disease has been approached in various ways, by the scientific community. Recent studies focus on individualized treatments, minimizing the undesirable consequences of the conventional methods, but the development of an alternative effective therapeutic scheme remains to be held. Nanomedicine could provide a solution, filling this gap, exploiting the unique properties of innovative nanostructured materials. Nanostructured titanium dioxide (TiO 2) has a variety of applications of daily routine and of advanced technology. Due to its biocompatibility, it has also a great number of biomedical applications. It is now clear that photoexcited TiO 2 nanoparticles, induce generation of pairs of electrons and holes which react with water and oxygen to yield reactive oxygen species (ROS) that have been proven to damage cancer cells, triggering controlled cellular processes. The aim of this review is to provide insights into the field of nanomedicine and particularly into the wide context of TiO 2-NP-mediated anticancer effect, shedding light on the achievements of nanotechnology and proposing this nanostructured material as a promising anticancer photosensitizer.
Biocompatibility of TiO2 prolate nanospheroids as a potential photosenzitizer in therapy of cancer
Journal of Nanoparticle Research, 2020
TiO 2 prolatenanospheroids (PNSs) may be photosensitizers (PSs), which act by catalyzation of hydroxyl radical (• OH) formation upon light illumination. • OH might, in turn, contribute to killing of cancer cells. On the other hand, there is great concern about toxicity in the dark of TiO 2 nanoparticles in general. In this work, we have investigated the biocompatibility of TiO 2 PNSs of the anatase crystal form (length between 100 and 300 nm and width 50 nm) in the dark with immune cells and lightinduced cytotoxicity on several cancer cell lines. The effects of the treatment of different cell lines with several concentrations of TiO 2 PNSs suspensions showed the specifics of cells' viability and the intracellular localization. The results of in vitro studies obtained by cytotoxicity assays adjusted to individual cell lines' metabolism point towards the biocompatibility of TiO 2 PNSs at low and moderate concentrations in the dark, which neither kill the cells, nor induce activation of the immune system cells. Laser scanning confocal microscopy revealed that PNSs are taken up by cells, and insight into the intracellular distribution was obtained in this study.
TiO2 Nanoparticle as a sensitizer drug in radiotherapy: in vitro study
Background: Radiosensitizer drugs are used to enhance the efficiency of radiotherapy. Some nanoparticles can be considered as radiosensitizers, because they enhance cytotoxicity due to oxidative stress and increase free radical yield, especially ROS, within cells resulting to cell death. Methods: In this study, synergistic effect of TiO2 nanoparticles was evaluated in presence of 60Co gamma rays on human breast cancer (MCF-7) and gastric cancer (MKN-45) cell lines. After cell culture, cells were exposed to several doses of gamma rays and a dose of 2Gy was selected due to survival analysis. Next, several doses of nanoparticle from each type was applied and cell survival was analyzed from which a dose of 30µg/ml was selected for the remainder of study. Finally, synergistic effect of gamma rays and nanoparticles was evaluated in two time delay groups using MTT assay. Results: Viability of cells in presence of gamma radiation and nanoparticles, significantly reduced compared to viability of cells exposed only to radiation or nanoparticle, alone (P-value≤0.05). The effect was dependent on nanoparticle type, time between addition of nanoparticle to cells and exposure to gamma rays and also cell dependent. Conclusion: TiO2 increased sensitivity of cancer cells to gamma radiation, due to an increase in ROS production and cytotoxicity. Anatase crystals have more severe effects than Rutile crystal because of having a larger surface area and creation of more free radicals. Therefore, this nanoparticle has the potential to be used as a radiosensitizer and further studies should be considered on other cell lines and in vivo.
Surface chemistry influences cancer killing effect of TiO2 nanoparticles
Nanomedicine: Nanotechnology, Biology and Medicine, 2008
Photocatalyzed titanium dioxide (TiO 2 ) nanoparticles have been shown to eradicate cancer cells. However, the required in situ introduction of ultraviolet light limits the use of such a therapy in humans. In the present study the nonphotocatalyic anticancer effect of surface-functionalized TiO 2 was examined. Nanoparticles bearing -OH, -NH 2 , or -COOH surface groups were tested for their effect on in vitro survival of several cancer and control cell lines. The cells tested included B16F10 melanoma, Lewis lung carcinoma, JHU prostate cancer cells, and 3T3 fibroblasts. Cell viability was observed to depend on particle concentrations, cell types, and surface chemistry. Specifically, -NH 2 and -OH groups showed significantly higher toxicity than -COOH. Microscopic and spectrophotometric studies revealed nanoparticle-mediated cell membrane disruption leading to cell death. The results suggest that functionalized TiO 2 , and presumably other nanoparticles, can be surfaceengineered for targeted cancer therapy.
Biomaterials, 2006
The appearance of drug-resistant (especially, multidrug-resistant (MDR)) tumor cells is a major obstacle to the success of chemotherapy; thus, the development of effective anti-MDR agents plays an important role in the tumor therapy. In this report, the considerable effect of nano-TiO 2 and UV illumination on the drug resistance of target cancer cells has been explored, and the fresh evidence from the fluorescence spectroscopy and microscopy as well as electrochemical studies demonstrates the significant enhancement effect of nano-TiO 2 to the drug uptake by drug-resistant leukemia cells. Besides, it is also observed that the combination of the nano-TiO 2 and UV irradiation with the accompanying anticancer drug daunorubicin could provoke some considerable changes of the cell membrane of the target leukemia cells, which indicates that nano-TiO 2 could not only increase the drug accumulation in target cancer cells, but also act as an effective anti-MDR agent to inhibit the relative drug resistance. r
Saudi Journal of Biological Sciences, 2021
Some nanoscale morphologies of titanium oxide nanostructures blend with gold nanoparticles and act as satellites and targeted weapon methodologies in biomedical applications. Simultaneously, titanium oxide can play an important role when combined with gold after blending with polyethylene glycol (PEG). Our experimental approach is novel with respect to the plasmonic role of metal nanoparticles as an efficient PDT drug. The current experimental strategy floats the comprehensive and facile way of experimental strategy on the critical influence that titanium with gold nanoparticles used as novel photosensitizing agents after significant biodistribution of proposed nanostructures toward targeted site. In addition, different morphologies of PEG-coated Au-doped titanium nanostructures were shown to provide various therapeutic effects due to a wide range of electromagnetic field development. This confirms a significantly amplified population of hot electron generation adjacent to the interface between Au and TiO 2 nanostructures, leading to maximum cancerous cell injury in the MCF-7 cell line. The experimental results were confirmed by applying a least squares fit math model which verified our results with 99% goodness of fit. These results can pave the way for comprehensive rational designs for satisfactory response of performance phototherapeutic model mechanisms along with new horizons of photothermal therapy (HET) and photodynamic therapy (HET) operating under visible and near-infrared (NIR) light.