Polymer-grafted gold nanoparticles for cancer treatment: synthesis and evaluation of their radiosensitizing properties

International audienceToday, even though treatments have much improved, cancer is still a leading cause of death in the world, being responsible for 1 death out of 6. Radiotherapy is widely used for tumor treatment, but suffers from side effects due to the irradiation of healthy surrounding tissues. Another issue is the radioresistance developed by some tumor cells, which implies to increase the involved doses. The challenge remains to deliver curative doses to tumor tissues while sparing sound ones. Hence the use of tumor-located radiosensitizers is a promising way to improve the efficacy of radiotherapy. High-Z materials have been known for several decades to amplify the damaging effects of both photon and ion radiations. Various nanoparticles have already been developed to take advantage of this property: gold, platinum and gadolinium are amongst the most investigated elements. A well-controlled synthesis is key to obtain stable and scalable nano-objects. Here, various polymers were grafted onto metallic nanoparticles to improve stability and biocompatibility and to facilitate subsequent functionalization. Advanced methods of characterization attested both robustness and reproducibility of the synthesis procedure. Moreover, promising results were obtained regarding the radioenhancing properties of these hybrid nanocompounds. Therefore, special attention has been given to the underlying mechanisms of the assessed radiosensitization, since they are not fully understood yet. Synthesis of polymer-grafted gold nanoparticles was performed through an in situ method, via the reduction of gold salts in the presence of polymeric ligands mainly prepared using controlled radical polymerization. The resulting nano-objects were fully characterized by thermogravimetric analysis, inductively coupled plasma mass spectrometry (ICP-MS), transmission electronic microscopy and small-angle x-ray and neutron scattering. Interactions between our nanocompounds and biological systems were studied in order to better understand the mechanisms at play. At the cellular scale, three aspects were examined for each type of nanoparticles: cellular uptake, cytotoxicity and radiosensitizing properties, through ICP-MS measurements, cell proliferation assays and clonogenic assays respectively. All irradiations were performed while keeping the delivered doses to low values (under 30 Gy) that are typical of clinic reality. Different types of radiations were tested, in order to compare their effects and their synergy with the nanocompounds. The synthesized nano-objects have shown great potential to enhance radiation cancer treatment. Their stability and controlled surface chemistry have allowed to develop multiple strategies in order to optimize their radiosensitizing effect and in vitro behavior

Selective Deposition and Alignment of Single-Walled Carbon Nanotubes Assisted by Dielectrophoresis: From Thin Films to Individual Nanotubes

Dielectrophoresis has been used in the controlled deposition of single-walled carbon nanotubes (SWNTs) with the focus on the alignment of nanotube thin films and their applications in the last decade. In this paper, we extend the research from the selective deposition of SWNT thin films to the alignment of small nanotube bundles and individual nanotubes. Electrodes with “teeth”-like patterns are fabricated to study the influence of the electrode width on the deposition and alignment of SWNTs. The entire fabrication process is compatible with optical lithography-based techniques. Therefore, the fabrication cost is low, and the resulting devices are inexpensive. A series of SWNT solutions is prepared with concentrations ranging from 0.0125 to 0.2 mg/ml. The alignment of SWNT thin films, small bundles, and individual nanotubes is achieved under the optimized experimental conditions. The electrical properties of these samples are characterized; the linear current–voltage plots prove that the aligned SWNTs are mainly metallic nanotubes. The microscopy inspection of the samples demonstrates that the alignment of small nanotube bundles and individual nanotubes can only be achieved using narrow electrodes and low-concentration solutions. Our investigation shows that it is possible to deposit a controlled amount of SWNTs in desirable locations using dielectrophoresis

On the distinctive call of a threatened phenotype of Allobates femoralis (Anura: Aromobatidae) and its recognition by allopatric conspecific males

ABSTRACT The brilliant-thighed frog [Allobates femoralis (Boulenger, 1884)]; is distributed across the Amazon basin and aggregates several allopatric evolutionary lineages, some of which present variation in their advertisement calls. In 2009, an unregistered call phenotype was discovered in the region of Altamira and Vitória do Xingu, State of Pará, Brazil, where males emit advertisement calls formed by six notes, differing from the typical four-note calls described for other A. femoralis populations. In this study, we describe in detail these untypical calls. Additionally, we test whether the aggressive responses of males of a 4-note reference population (Reserva Ducke - RFAD, in Manaus, State of Amazonas) is differential towards the 6-note calls of males recorded in Altamira (Pará State), and towards 4-note calls recorded in one location at the Tapajós-Xingu interfluve (Belterra, Pará State), and in RFAD. Playback experiments were conducted between 2011-2012, and used standardized stimuli produced from natural call recordings. A total of 30 independent experiments were conducted, 10 for each stimuli class. We measured the phonotaxis of focal males in relation to the loudspeaker, considering the time to orientation and the time to approach the loudspeaker. We found that not all A. femoralis males at RFAD promptly recognize calls from males recorded in Altamira. However, when considering only males who approached the loudspeaker, differences in aggressive reactions were not seen between stimuli classes. Our findings show that the ability to recognize calls from Altamira as belonging to co-specific males is not universal among males at RFAD. The new A. femoralis phenotype occurs in areas potentially impacted by the Belo Monte hydroelectric complex and complementary studies indicate that no gene flow exists between this group and A. femoralis from adjacent regions. Hence, developments in Altamira may put this incipient speciation process at risk

3D printed tubulanes as lightweight hypervelocity impact resistant structures

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORLightweight materials with high ballistic impact resistance and load-bearing capabilities are regarded as a holy grail in materials design. Nature builds these complementary properties into materials using soft organic materials with optimized, complex geometries. Here, the compressive deformation and ballistic impact properties of three different 3D printed polymer structures, named tubulanes, are reported, which are the architectural analogues of cross-linked carbon nanotubes. The results show that macroscopic tubulanes are remarkable high load-bearing, hypervelocity impact-resistant lightweight structures. They exhibit a lamellar deformation mechanism, arising from the tubulane ordered pore structure, manifested across multiple length scales from nano to macro dimensions. This approach of using complex geometries inspired by atomic and nanoscale models to generate macroscale printed structures allows innovative morphological engineering of materials with tunable mechanical responses.155219CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORSem informação2013/08293-7001The authors would like to acknowledge Aramco Research Center for funding this research (Grant number: 1137681). D.S.G. and C.F.W. acknowledge support from Brazilian agencies CNPq and FAPESP (number 2013/08293-7). This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES)-Finance Code 001