Using synchrotron radiation-based circular dichroism spectroscopy, we found that the DNA damage response induces an increase of α-helix structure and a decrease of β-strand and turn structures in histone H2A-H2B extracted from x-irradiated human HeLa cells. The structural alterations correspond to the assumption that an average of eight amino acid residues form new α-helix structures at 310 K. We propose the structural transition from β-strand and turn structures to an α-helix structure in H2A-H2B as a novel, to our knowledge, process involved in the DNA damage response.

Nanomedicine has stepped into the spotlight of radiation therapy over the last two decades. Nanoparticles (NPs), especially metallic NPs, can potentiate radiotherapy by specific accumulation into tumors, thus enhancing the efficacy while alleviating the toxicity of radiotherapy. Water radiolysis is a simple, fast and environmentally-friendly method to prepare highly controllable metallic nanoparticles in large scale. In this study, we used this method to prepare biocompatible PEGylated (with Poly(Ethylene Glycol) diamine) platinum nanoflowers (Pt NFs). These nanoagents provide unique surface chemistry, which allows functionalization with various molecules such as fluorescent markers, drugs or radionuclides. The Pt NFs were produced with a controlled aggregation of small Pt subunits through a combination of grafted polymers and radiation-induced polymer cross-linking. Confocal microscopy and fluorescence lifetime imaging microscopy revealed that Pt NFs were localized in the cytoplasm of cervical cancer cells (HeLa) but not in the nucleus. Clonogenic assays revealed that Pt NFs amplify the gamma rays induced killing of HeLa cells with a sensitizing enhancement ratio (SER) of 23%, thus making them promising candidates for future cancer radiation therapy. Furthermore, the efficiency of Pt NFs to induce nanoscopic biomolecular damage by interacting with gamma rays, was evaluated using plasmids as molecular probe. These findings show that the Pt NFs are efficient nano-radio-enhancers. Finally, these NFs could be used to improve not only the performances of radiation therapy treatments but also drug delivery and/or diagnosis when functionalized with various molecules.

The use of nanoparticles, in combination with ionizing radiation, is considered a promising method to improve the performance of radiation therapies. In this work, we engineered mono- and bimetallic core-shell gold–platinum nanoparticles (NPs) grafted with poly (ethylene glycol) (PEG). Their radio-enhancing properties were investigated using plasmids as bio-nanomolecular probes and gamma radiation. We found that the presence of bimetallic Au:Pt-PEG NPs increased by 90% the induction of double-strand breaks, the signature of nanosize biodamage, and the most difficult cell lesion to repair. The radio-enhancement of Au:Pt-PEG NPs were found three times higher than that of Au-PEG NPs. This effect was scavenged by 80% in the presence of dimethyl sulfoxide, demonstrating the major role of hydroxyl radicals in the damage induction. Geant4-DNA Monte Carlo simulations were used to elucidate the physical processes involved in the radio-enhancement. We predicted enhancement factors of 40% and 45% for the induction of nanosize damage, respectively, for mono- and bimetallic nanoparticles, which is attributed to secondary electron impact processes. This work contributed to a better understanding of the interplay between energy deposition and the induction of nanosize biomolecular damage, being Monte Carlo simulations a simple method to guide the synthesis of new radio-enhancing agents.

Metal-based nanoparticles are widely used to deliver bioactive molecules and drugs to improve cancer therapy. Several research works have highlighted the synthesis of gold and silver nanoparticles by green chemistry, using biological entities to minimize the use of solvents and control their physicochemical and biological properties. Recent advances in evaluating the anticancer effect of green biogenic Au and Ag nanoparticles are mainly focused on the use of conventional 2D cell culture and in vivo murine models that allow determination of the half-maximal inhibitory concentration, a critical parameter to move forward clinical trials. However, the interaction between nanoparticles and the tumor microenvironment is not yet fully understood. Therefore, it is necessary to develop more human-like evaluation models or to improve the existing ones for a better understanding of the molecular bases of cancer. This review provides recent advances in biosynthesized Au and Ag nanoparticles for seven of the most common and relevant cancers and their biological assessment. In addition, it provides a general idea of the in silico, in vitro, ex vivo, and in vivo models used for the anticancer evaluation of green biogenic metal-based nanoparticles.

The gadolinium-based nanoagent named AGuIX® is a unique radiosensitizer and contrast agent which improves the performance of radiotherapy and medical imaging. Currently tested in clinical trials, AGuIX® is administrated to patients via intravenous injection. The presence of nanoparticles in the blood stream may induce harmful effects due to undesired interactions with blood components. Thus, there is an emerging need to understand the impact of these nanoagents when meeting blood proteins. In this work, the influence of nanoagents on the structure and stability of the most abundant blood protein, human serum albumin, is presented. Synchrotron radiation circular dichroism showed that AGuIX® does not bind to the protein, even at the high ratio of 45 nanoparticles per protein at 3 mg/L. However, it increases the stability of the albumin. Isothermal thermodynamic calorimetry and fluorescence emission spectroscopy demonstrated that the effect is due to preferential hydration processes. Thus, this study confirms that intravenous injection of AGuIX® presents limited risks of perturbing the blood stream. In a wider view, the methodology developed in this work may be applied to rapidly evaluate the impact and risk of other nano-products that could come into contact with the bloodstream.

Purpose: Metal-based nanoparticles (M-NPs) have attracted great attention in nanomedicine due to their capacity to amplify and improve the tumor targeting of medical beams. However, their simple, efficient, high-yield and reproducible production remains a challenge. Currently, M-NPs are mainly synthesized by chemical methods or radiolysis using toxic reactants. The waste of time, loss of material and potential environmental hazards are major limitations. Materials and Methods: This work proposes a simple, fast and green strategy to synthesize small, non-toxic and stable NPs in water with a 100% production rate. Ionizing radiation is used to simultaneously synthesize and sterilize the containing NPs solutions. The synthesis of platinum nanoparticles (Pt NPs) coated with biocompatible poly(ethylene glycol) ligands (PEG) is presented as proof of concept. The physicochemical properties of NPs were studied by complementary specialized techniques. Their toxicity and radio-enhancing properties were evaluated in a cancerous in vitro model. Using plasmid nanoprobes, we investigated the elementary mechanisms underpinning radio-enhancement. Results and Discussion: Pt NPs showed nearly spherical-like shapes and an average hydrodynamic diameter of 9 nm. NPs are zero-valent platinum successfully coated with PEG. They were found non-toxic and have the singular property of amplifying cell killing induced by γ-rays (14%) and even more, the effects of carbon ions (44%) used in particle therapy. They induce nanosized-molecular damage, which is a major finding to potentially implement this protocol in treatment planning simulations. Conclusion: This new eco-friendly, fast and simple proposed method opens a new era of engineering water-soluble biocompatible NPs and boosts the development of NP-aided radiation therapies.

Hydroxyapatite (HAp) is a natural hard tissue constituent widely used for bone and tooth replacement engineering. In the present work, synthetic HAp was obtained from calcium nitrate tetrahydrate (Ca(NO3)2·4H2O) and ammonium phosphate dibasic (NH4)2HPO4 following an optimized microwave assisted hydrothermal method. The effect of pH was evaluated by the addition of ammonium hydroxide (NH4OH). Hence, different characterization techniques were used to determine its influence on the resulted HAp powders’ size, shape, and crystallinity. By Transmission Electron Microscopy (TEM), it was observed that the reaction pH environment modifies the morphology of HAp, and a shape evolution, from sub-hedral particles at pH = 7 to rod-like nanosized HAp at pH = 10, was confirmed. Using the X-ray Diffraction (XRD) technique, the characteristic diffraction peaks of the monoclinic phase were identified. Even if the performed Rietveld analysis indicated the presence of both phases (hexagonal and monoclinic), monoclinic HAp prevails in 95% with an average crystallite size of about 23 nm. The infrared spectra (FTIR) showed absorption bands at 3468 cm−1 and 630 cm−1 associated with OH− of hydroxyapatite, and bands at 584 cm−1, 960 cm−1, and 1090 cm−1 that correspond to the PO43− and CO32− characteristic groups. In summary, this work contributes to obtaining nanosized rod-like monoclinic HAp by a simple and soft method that has not been previously reported.

La hidroxiapatita nanoestructurada (nano-Hap) surge como una potente herramienta biomimética para mejorar el desempeño de las terapias convencionales contra el cáncer. Su composición química, textura y capacidad de dopaje, así como su compatibilidad, estabilidad y actividad en sistemas biológicos la hacen una candidata excepcional para el desarrollo de vehículos para la entrega selectiva de fármacos antineoplásicos. La presente revisión va dirigida a estudiantes e investigadores del área de materiales avanzados, con la intensión de introducirlos en la importancia de explorar de manera interdisciplinaria las propiedades intrínsecas y adquiridas de los nanomateriales en beneficio de la sociedad, principalmente para ciencias de la salud. Con un propósito formativo, presentamos generalidades de la síntesis, caracterización y evaluación toxicológica in vitro de la nano-Hap para, finalmente discutir los avances más relevantes en el área del 2016 a la fecha. Concluimos incentivando a la comunidad al trabajo colaborativo interdisciplinar para innovar en Nanomedicina con materiales que permitan mejorar el desempeño de los protocolos oncológicos existentes.