In vivo evaluation of a hybrid nanoparticle for molecular imaging of amyloid aggregation

International audienceAmyloid-β (Aβ) fibrillization is described as a central event in the pathogenesis of Alzheimer’s disease (AD). Amyloid imaging is expected to play a pivotal role in early and differential diagnosis of dementias, and in the evaluation of anti-Aβ treatments. Luminescent conjugated oligothiophenes (LCO) have been proposed as optical biomarkers of protein fibrillation [1]. In this paper, we evaluated a fluorescent magnetic hybrid nanoprobe (HNP5011), based on gadolinium fluoride nanoparticles functionalized with luminescent conjugated polythiophenes moieties (Fig. 1). The aim of this study was to investigate its potential for molecular imaging in a rat model bearing intracerebral pre-aggregated Aβ peptides

From gold nanobipyramids to nanojavelins for a precise tuning of the plasmon resonance to the infrared wavelengths: experimental and theoretical aspects

International audienceAnisotropic gold nanoparticles and in particular with shapes exhibiting tips are known to present an extremely strong localized electromagnetic field. This field is mostly located at the top of the tips and can be used in various optical applications. Moreover, as a consequence of their anisotropy, they present two plasmon resonance bands corresponding to the transverse and longitudinal resonance modes. Tuning the aspect ratio it becomes possible to display SPR bands near the near infrared region. This was particularly investigated in the case of nanorods and also for bipyramids. In this paper we report a high yield synthesis approach that allows one to precisely control the aspect ratio of bipyramids and to elongate the structure until they adopt a javelin-like aspect. We were able to prepare nano-javelins with surface plasmon resonances up to 1850 nm, opening important perspectives in terms of optical applications in the NIR and IR regions. The synthetic methods are fully reported and the optical properties were correlated with the theoretical approach, taking into consideration not only the aspect ratio but also the truncation of the nano-objects

From gold nanobipyramids to nanojavelins for a precise tuning of the plasmon resonance to the infrared wavelengths: experimental and theoretical aspects

International audienceAnisotropic gold nanoparticles and in particular with shapes exhibiting tips are known to present an extremely strong localized electromagnetic field. This field is mostly located at the top of the tips and can be used in various optical applications. Moreover, as a consequence of their anisotropy, they present two plasmon resonance bands corresponding to the transverse and longitudinal resonance modes. Tuning the aspect ratio it becomes possible to display SPR bands near the near infrared region. This was particularly investigated in the case of nanorods and also for bipyramids. In this paper we report a high yield synthesis approach that allows one to precisely control the aspect ratio of bipyramids and to elongate the structure until they adopt a javelin-like aspect. We were able to prepare nano-javelins with surface plasmon resonances up to 1850 nm, opening important perspectives in terms of optical applications in the NIR and IR regions. The synthetic methods are fully reported and the optical properties were correlated with the theoretical approach, taking into consideration not only the aspect ratio but also the truncation of the nano-objects

Investigation of a fluorescent magnetic hybrid nanoprobe for stroke imaging

International audienceIntroduction In this paper, we introduce a fluorescent magnetic hybrid nanoprobe (5011), based on gadolinium fluoride nanoparticles functionalized with luminescent conjugated polythiophenes moieties (Fig 1). The aim of this study was to investigate its potential for molecular imaging in experimental stroke. Specifically, we aimed to test the hypothesis that 5011 may cross the disrupted blood-brain barrier (BBB) in the ischemic lesion. Methods Transient middle cerebral artery occlusion (tMCAO) was performed in 7 rats using the intraluminal model. In this model, mild BBB disruption was consistently shown at 3 days post-surgery (1). Therefore, dynamic MRI of the brain was performed 3 days post-tMCAO, before, during and after bolus injection of 5011 (N=6) or Gd-DOTA (N=1) both at 150 µmol Gd/kg (7T, TE/TR: 10.5/800-ms, flip angle 30°, 40 repetitions, one-hour acquisition). We used a model of focal BBB opening by heat injury (N=6) to ascertain that the MR sequence used was sensitive enough to detect contrast enhancement due to 5011 leakage through a severely disrupted BBB. Brains and livers of tMCAO rats were prepared either for biphotonic microscopy (N=3) or inductively coupled plasma-mass spectroscopy (ICP-MS, N=3). Results As expected in tMCAO rats, Gd-DOTA injection resulted in a significant enhancement of the ischemic lesion (22% compared to pre-contrast signal). In contrast, there was no signal enhancement difference between the ischemic lesion (-3±1%) and the contralateral region (-2±1%) in rats injected with 5011 (Fig 2A). Biphotonic microscopy showed sparse agglomerates of 5011 in the parenchyma of the ischemic lesion (Fig 2, insert). In the model of focal BBB opening, 5011 injection resulted in a significant enhancement of the lesion (13±3%) (Fig 2B). ICP-MS analyses are in progress. Conclusions Transport of 5011 across the disrupted BBB could be detected in tMCAO rats using a sensitive two-photon microscope but its accumulation was too low to be detected with MRI. Based on these results, we aim to functionalize the hybrid nanoprobe to target vascular adhesion molecules that are highly expressed after experimental stroke, rather than intraparenchymal (extravascular) targets

Investigation of a fluorescent magnetic hybrid nanoprobe for stroke imaging

International audienceIntroduction In this paper, we introduce a fluorescent magnetic hybrid nanoprobe (5011), based on gadolinium fluoride nanoparticles functionalized with luminescent conjugated polythiophenes moieties (Fig 1). The aim of this study was to investigate its potential for molecular imaging in experimental stroke. Specifically, we aimed to test the hypothesis that 5011 may cross the disrupted blood-brain barrier (BBB) in the ischemic lesion. Methods Transient middle cerebral artery occlusion (tMCAO) was performed in 7 rats using the intraluminal model. In this model, mild BBB disruption was consistently shown at 3 days post-surgery (1). Therefore, dynamic MRI of the brain was performed 3 days post-tMCAO, before, during and after bolus injection of 5011 (N=6) or Gd-DOTA (N=1) both at 150 µmol Gd/kg (7T, TE/TR: 10.5/800-ms, flip angle 30°, 40 repetitions, one-hour acquisition). We used a model of focal BBB opening by heat injury (N=6) to ascertain that the MR sequence used was sensitive enough to detect contrast enhancement due to 5011 leakage through a severely disrupted BBB. Brains and livers of tMCAO rats were prepared either for biphotonic microscopy (N=3) or inductively coupled plasma-mass spectroscopy (ICP-MS, N=3). Results As expected in tMCAO rats, Gd-DOTA injection resulted in a significant enhancement of the ischemic lesion (22% compared to pre-contrast signal). In contrast, there was no signal enhancement difference between the ischemic lesion (-3±1%) and the contralateral region (-2±1%) in rats injected with 5011 (Fig 2A). Biphotonic microscopy showed sparse agglomerates of 5011 in the parenchyma of the ischemic lesion (Fig 2, insert). In the model of focal BBB opening, 5011 injection resulted in a significant enhancement of the lesion (13±3%) (Fig 2B). ICP-MS analyses are in progress. Conclusions Transport of 5011 across the disrupted BBB could be detected in tMCAO rats using a sensitive two-photon microscope but its accumulation was too low to be detected with MRI. Based on these results, we aim to functionalize the hybrid nanoprobe to target vascular adhesion molecules that are highly expressed after experimental stroke, rather than intraparenchymal (extravascular) targets

Investigation of a fluorescent magnetic hybrid nanoprobe for stroke imaging

International audienceIntroduction In this paper, we introduce a fluorescent magnetic hybrid nanoprobe (5011), based on gadolinium fluoride nanoparticles functionalized with luminescent conjugated polythiophenes moieties (Fig 1). The aim of this study was to investigate its potential for molecular imaging in experimental stroke. Specifically, we aimed to test the hypothesis that 5011 may cross the disrupted blood-brain barrier (BBB) in the ischemic lesion. Methods Transient middle cerebral artery occlusion (tMCAO) was performed in 7 rats using the intraluminal model. In this model, mild BBB disruption was consistently shown at 3 days post-surgery (1). Therefore, dynamic MRI of the brain was performed 3 days post-tMCAO, before, during and after bolus injection of 5011 (N=6) or Gd-DOTA (N=1) both at 150 µmol Gd/kg (7T, TE/TR: 10.5/800-ms, flip angle 30°, 40 repetitions, one-hour acquisition). We used a model of focal BBB opening by heat injury (N=6) to ascertain that the MR sequence used was sensitive enough to detect contrast enhancement due to 5011 leakage through a severely disrupted BBB. Brains and livers of tMCAO rats were prepared either for biphotonic microscopy (N=3) or inductively coupled plasma-mass spectroscopy (ICP-MS, N=3). Results As expected in tMCAO rats, Gd-DOTA injection resulted in a significant enhancement of the ischemic lesion (22% compared to pre-contrast signal). In contrast, there was no signal enhancement difference between the ischemic lesion (-3±1%) and the contralateral region (-2±1%) in rats injected with 5011 (Fig 2A). Biphotonic microscopy showed sparse agglomerates of 5011 in the parenchyma of the ischemic lesion (Fig 2, insert). In the model of focal BBB opening, 5011 injection resulted in a significant enhancement of the lesion (13±3%) (Fig 2B). ICP-MS analyses are in progress. Conclusions Transport of 5011 across the disrupted BBB could be detected in tMCAO rats using a sensitive two-photon microscope but its accumulation was too low to be detected with MRI. Based on these results, we aim to functionalize the hybrid nanoprobe to target vascular adhesion molecules that are highly expressed after experimental stroke, rather than intraparenchymal (extravascular) targets

Students' design of a biometric procedure in upper secondary school

International audienceMaking the connection between science and technology might be important for students to learn to identify and solve problems and to acquire scientific knowledge and skills. The research reported in this article concerned the development of a design situation in a science classroom and the study of students performing in this situation. More specifically, the setting involved students' design of a measurement procedure as a way of attaining understanding of the underlying scientific concepts. In fact, at higher secondary level, the classical experimental procedure of measuring facial angle is employed within the topic of human evolution to find out to which species a given human cranium belongs. At the same time, designing a procedure, instead of just executing it, is thought to entail higher odds for attaining teleological understanding. The development of the learning situation involved pursuing parallels between the expert design task as described in the literature and the assignment given to students. We proceeded through step-wise development of the learning situation that was successively tested out in the classroom. Our analysis of the student-devised procedures revealed three issues regarding the graphical representation of angles, the reproducibility of the points and the communicational demands of the situation. Students used both prior knowledge (e.g. about evolution), and new knowledge about cranium anatomy and angles. They also exhibited new experimental skills like anticipating each experimental action. Such cognitive tasks which are at the origin of students' activity make the situation approximate the goals of laboratory work by distancing it from the simple execution of a series of steps. Future research could be directed towards further exploring the benefits of an approach that combines essential characteristics of science and technology