A synchrotron-based infrared microspectroscopy study on the cellular response induced by gold nanoparticles combined with X-ray irradiations on F98 and U87-MG glioma cell lines

The inclusion of nanoparticles (NP) in radiotherapy has been shown to increase the damaging effect on tumor cells. However, the mechanisms of action of NP combined with radiotherapy, and the influence of NP parameters and cell type on their radiosensitization capability at molecular and cellular levels still remain unclear. Gold NP (AuNP) have become particularly popular due to their multiple advantages. Within this context, our research work aimed to study the biochemical radiosensitization capacity of F98 and U87-MG glioma cell lines to 1.9 nm AuNP combined with X-ray irradiation. For this purpose, synchrotron-based infrared microspectroscopy (SR-FTIRM) was used as a powerful tool for biochemical composition and treatment response assessment of cells at a single-cell level. SR-FTIRM data, supported by multivariate analysis, revealed clear AuNP-induced changes in the DNA, protein and lipid spectral regions. The AuNP-related biochemical alterations appear prior to the irradiation, which gave us a first indication on the AuNP radiosensitization action. Biochemical modifications induced by the AuNP in the presence of radiotherapy irradiations include enhanced conformational changes in the protein secondary structures, variations in the intensity and position in the phosphodiester bands, and changes in the CH2 and CH3 stretching modes. These changes are better manifested at 24 hours post-irradiation time. SR-FTIRM results showed a clear heterogeneity in the biochemical cell response, probably due to the distinct cell-NP interactions and thus, to different DNA damage and cell death processes

Synchrotron-based infrared microspectroscopy study on the radiosensitization effects of Gd nanoparticles at megavoltage radiation energies

The outcome of radiotherapy can be further improved by combining radiotherapy with nanoparticles. Previous biological studies showed a significant amplification of the biological damage in cells charged with nanoparticles prior to radiotherapy treatments. The rationale has been based on the physical dose enhancement. However, this subject is still a matter of controversy and there are clear indications that biochemical effects may play a key role in the radiosensitization effects of nanoparticles. Within this context, the main goal of our study was to provide new insights into the radiosensitization effects of F98 glioma cells exposed to gadolinium nanoparticles combined with clinical megavoltage beams, and compare them with respect to kilovoltage radiotherapy (commonly used in combination with nanoparticles). For this purpose, we used synchrotron-based Fourier transform infrared microspectroscopy (SR-FTIRM) to provide relevant information on the treatment-induced biochemical changes of the main cell biomolecules. Biochemical differences were evaluated after the treatments to assess cellular damage. Multivariate analysis revealed nanoparticle-dependent changes in megavoltage treated cells. The main spectral variations were related to conformational changes in the protein secondary structures, which might be induced by radiation damage and by changes or rearrangements in the nucleic acid structures due to the initiation of DNA repair mechanisms. We also observed significant changes in the phosphate I and II bands, which concerns DNA damage, while few changes were detected in the lipid region. Spectroscopic data showed that these changes increased as a function of the dose. Finally, PCA analysis did not discriminate clearly between megavoltage and kilovoltage groups treated with nanoparticles, indicating that megavoltage radiosensitization effects might not differ significantly from those in kilovoltage radiotherapy

A synchrotron-based infrared microspectroscopy study on the cellular response induced by gold nanoparticles combined with X-ray irradiations on F98 and U87-MG glioma cell lines

The inclusion of nanoparticles (NP) in radiotherapy has been shown to increase the damaging effect on tumor cells. However, the mechanisms of action of NP combined with radiotherapy, and the influence of NP parameters and cell type on their radiosensitization capability at molecular and cellular levels still remain unclear. Gold NP (AuNP) have become particularly popular due to their multiple advantages. Within this context, our research work aimed to study the biochemical radiosensitization capacity of F98 and U87-MG glioma cell lines to 1.9 nm AuNP combined with X-ray irradiation. For this purpose, synchrotron-based infrared microspectroscopy (SR-FTIRM) was used as a powerful tool for biochemical composition and treatment response assessment of cells at a single-cell level. SR-FTIRM data, supported by multivariate analysis, revealed clear AuNP-induced changes in the DNA, protein and lipid spectral regions. The AuNP-related biochemical alterations appear prior to the irradiation, which gave us a first indication on the AuNP radiosensitization action. Biochemical modifications induced by the AuNP in the presence of radiotherapy irradiations include enhanced conformational changes in the protein secondary structures, variations in the intensity and position in the phosphodiester bands, and changes in the CH2 and CH3 stretching modes. These changes are better manifested at 24 hours post-irradiation time. SR-FTIRM results showed a clear heterogeneity in the biochemical cell response, probably due to the distinct cell-NP interactions and thus, to different DNA damage and cell death processes

Synchrotron-Based Infrared Microscopy Studies of the Radiosensitization Effects of Nanoparticles used in Radiotherapy

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A Fluorescent Nanoprobe to Detect Local Temperature Changes During Antitumoral Hyperthermia Therapy

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Chains of Magnetosomes Extracted from AMB-1 Magnetotactic Bacteria for Application in Alternative Magnetic Field Cancer Therapy

International audienceChains of magnetosomes extracted from magnetotactic bacteria are shown to be highly efficient for alternative magnetic field cancer therapy. The viability of MDA-MB-231 breast cancer cells is relatively unaffected by the presence of less than ∼ 1 mg of chains of magnetosomes. When these cells are exposed to an oscillating magnetic field of frequency 183 kHz and field strengths of 20 to 60 mT, up to 100 % of them are destroyed. We show that it is possible to fully eradicate a tumor xeno-greffed on a mouse by administering a suspension containing ∼ 1 mg of chains of magnetosomes within the tumor and by exposing the mouse to three heat cycles of 20 minutes, during which the tumor temperature is raised to ∼ 43°C. We demonstrate the higher efficiency of the chains of magnetosomes compared with various other materials, i. e. whole inactive magnetotactic bacteria, individual magnetosomes not organized in chains and two different types of chemically synthesized nanoparticles currently tested for alternative magnetic field cancer therapy. The efficiency of the chains of magnetosomes is attributed to three factors, (i), a high magnetosome specific absorption rate (SAR), (ii), a homogenous distribution of the chains of magnetosomes within the tumor yielding uniform heating and (iii), the faculty of the chains of magnetosomes to penetrate within the cancer cells following the application of the alternative magnetic field, which enables intra-cellular heating. Biodistribution studies reveal that chains of magnetosomes administered directly within xeno-greffed breast tumors progressively leave the tumors during the 14 days following their administration and are then eliminated in the feces

A Minimalistic in Vitro 3D Model to Study F98 Rat Brain Tumor Growth

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Fluorescent magnetosomes for controlled and repetitive drug release under the application of an alternating magnetic field under conditions of limited temperature increase (<2.5 °C)

International audienceTherapeutic substances bound to nanoparticles have been shown to dissociate following excitation by various external sources of energies or chemical disturbance, resulting in controllable and efficient antitumor activity. Bioconjugation is used to produce magnetosomes associated with Rhodamine B (RhB), whose fluorescence is partially quenched by the presence of iron oxide and becomes strongly enhanced when RhB dissociates from the magnetosomes under the application of an alternating magnetic field. This novel approach enables the release of a RhB model molecule while monitoring the mechanism by fluorescence. The dissociation mechanism of RhB is highlighted by exposing a suspension of fluorescent magnetosomes to an alternating magnetic field, by magnetically isolating the supernatant of this suspension, and by showing fluorescence enhancement of the supernatant. Furthermore, to approach in vivo conditions, fluorescent magnetosomes are mixed with tissue or introduced in the mouse brain and exposed to the alternating magnetic field. Most interestingly, the percentages of RhB dissociation measured at the beginning of magnetic excitation (ΔR/δt) or 600 seconds afterwards (R600 s) are ΔR/δt ∼ 0.13% and R600 s ∼ 50% under conditions of limited temperature increases (<2.5 °C), larger values than those of ΔR/δt ∼ 0.02–0.11% and R600 s ∼ 13%, estimated for temperature increase larger than 2.5 °C. Furthermore, when magnetic excitations are repeated two to five times, the temperature increase becomes undetectable, but RhB dissociation continues to occur up to the fifth magnetic excitation. Since high heating temperatures may be damaging for tissues, this study paves the way towards the development of a safe theranostic dissociating nano-probe operating under conditions of limited temperature increase

Modelling In Vitro Aggregation of Cancer Cells

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