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Cu-doped TiO₂ nanoparticles improve local antitumor immune activation and optimize dendritic cell vaccine strategies.

ABSTRACT: Nanoparticle-mediated cancer immunotherapy holds great promise, but more efforts are needed to obtain nanoformulations that result in a full scale activation of innate and adaptive immune components that specifically target the tumors. We generated a series of copper-doped TiO₂ nanoparticles in order to tune the kinetics and full extent of Cu²⁺ ion release from the remnant TiO₂ nanocrystals. Fine-tuning nanoparticle properties resulted in a formulation of 33% Cu-doped TiO₂ which enabled short-lived hyperactivation of dendritic cells and hereby promoted immunotherapy. The nanoparticles result in highly efficient activation of dendritic cells ex vivo, which upon transplantation in tumor bearing mice, exceeded the therapeutic outcomes obtained with classically stimulated dendritic cells. Efficacious but simple nanomaterials that can promote dendritic cancer cell vaccination strategies open up new avenues for improved immunotherapy and human health.

SUBMITTER: Hesemans E

PROVIDER: S-EPMC10009859 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Cu-doped TiO2 nanoparticles improve local antitumor immune activation and optimize dendritic cell vaccine strategies.

Hesemans Evelien E Saffarzadeh Neshat N Maksoudian Christy C Izci Mukaddes M Chu Tianjiao T Rios Luci Carla C Wang Yuqing Y Naatz Hendrik H Thieme Sebastian S Richter Cornelia C Manshian Bella B BB Pokhrel Suman S Mädler Lutz L Soenen Stefaan J SJ

Journal of nanobiotechnology 20230313 1

Nanoparticle-mediated cancer immunotherapy holds great promise, but more efforts are needed to obtain nanoformulations that result in a full scale activation of innate and adaptive immune components that specifically target the tumors. We generated a series of copper-doped TiO2 nanoparticles in order to tune the kinetics and full extent of Cu2+ ion release from the remnant TiO2 nanocrystals. Fine-tuning nanoparticle properties resulted in a formulation of 33% Cu- ...[more]

PMID: 36915084

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Project description:Copper-doped TiO2 was prepared with a sol-gel chemical method. Various concentrations (3, 6, and 9 wt%) of Cu dopant were employed. Several techniques were implemented to assess the structural, optical, morphological and chemical properties of the synthesized samples. Evaluation of elemental composition using SEM-EDS and XRF techniques showed the presence of dopant element in the prepared samples. XRD analysis confirmed the presence of anatase (TiO2) phase with interstitial doping. Incorporation of dopant was observed to enhance the crystallinity and increase the crystallite size of the synthesized products. SAED profiles revealed a high degree of crystallinity in the prepared specimens, which was also evident in the XRD spectra. Optical properties studied using UV-vis spectroscopy depicted a shift of the maximum absorption to the visible region (redshift) that signified a reduction in the band gap energy of Cu-doped TiO2 samples. Examination of morphological features with scanning and high-resolution transmission electron microscopes revealed the formation of spherical nanoparticles with a tendency to agglomerate with increasing dopant concentration. Molecular vibrations and the formation of Ti-O-Ti bonds were revealed through FTIR spectra. PL spectroscopy recorded the trapping efficiency and migration of charge carriers, which exhibited electron-hole recombination behavior. Doped nanostructures showed enhanced bactericidal performance and synergism against S. aureus and E. coli. In summary, Cu-doped TiO2 nanostructures were observed to impede bacteria effectively, which is deemed beneficial in overcoming ailments caused by pathogens such as microbial etiologies. Furthermore, molecular docking analysis was conducted to study the interaction of Cu-doped TiO2 nanoparticles with multiple proteins namely β-lactamase (binding score: -4.91 kcal mol-1), ddlB (binding score: -5.67 kcal mol-1) and FabI (binding score: -6.13 kcal mol-1) as possible targets with active site residues. Dye degradation/reduction of control and Cu-doped samples were studied through absorption spectroscopy. The obtained outcomes of the performed experiment indicated that the photocatalytic activity of Cu-TiO2 enhanced with increasing dopant concentration, which is thought to be due to a decreased rate of electron-hole pair recombination. Consequently, it is suggested that Cu-TiO2 can be exploited as an effective candidate for antibacterial and dye degradation applications.

Project description:Oxide based dilute magnetic semiconductor materials have been of great interest over the years due to their potential use in spintronic devices. However, the variations in the magnetic behavior of the materials have raised concerns regarding the origin of ferromagnetic properties which still needs to be explored. Manipulation of magnetic behavior in oxide based dilute magnetic semiconductors has become a challenge due to the interplay of intrinsic defects present in the material. TiO2 nanocrystals have been studied largely due to their challenging optical and magnetic properties. The present investigation studies in detail the structural, morphological, optical and magnetic behavior of non-magnetic element (Cu and Zn) doped TiO2, synthesized via a simple sol-gel technique. X-ray diffraction patterns and Raman spectra confirm the anatase phase and high resolution transmission electron microscopic results clearly indicate the formation of highly crystalline nanocrystals in all the samples with particle size ranging from 5-15 nm. Energy dispersive X-ray fluorescence spectroscopic studies reveal the compositional homogeneity of all the investigated samples. The presence of functional groups and molecular interactions were identified by Fourier transform infrared spectroscopy. Optical properties were studied through UV-visible and photoluminescence spectroscopy from which a significant reduction in band gap in Cu-doped TiO2 nanocrystals was found. X-ray photoelectron spectra confirm the presence of Ti3+, Cu2+, Cu+ and Zn2+ in Cu and Zn-doped TiO2 samples. The concept of bound magnetic polarons associated with the vacancy defects at both Ti, Cu, Zn and oxygen sites is used to explain the induced weak ferromagnetic behavior in undoped, Cu and Zn-doped TiO2 at room temperature. The overlapping of bound magnetic polarons could be the source of ferromagnetism irrespective of the non-magnetic nature of the dopant ion. The concentration of bound magnetic polarons is estimated using a Langevin fit and a detailed understanding of the variation of defect mediated magnetic properties is established with the help of PL analysis. A significant reduction in bandgap along with enhanced magnetization observed in the Cu-doped TiO2 material makes it suitable as a potential candidate for spintronics and magneto-optics applications. Room temperature magnetic properties of the Zn doped sample show a diamagnetic tail which is explained based on the defect centers and oxidation states of dopant ions present in the sample which is further verified with the help of XPS results.

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Cu-doped TiO₂ nanoparticles improve local antitumor immune activation and optimize dendritic cell vaccine strategies.

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Cu-doped TiO<sub>2</sub> nanoparticles improve local antitumor immune activation and optimize dendritic cell vaccine strategies.

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