Electrophoretic impregnation of porous anodic aluminum oxide film by silica nanoparticles

In this paper, it is proposed to study the deposition of nanoparticles by electrophoretic deposition (EPD) inside a porous anodic aluminum oxide film. Despite the presence of a highly resistive barrier layer at the metal-anodic film interface, porous anodic films on AA 1050A were successfully filled by 16-nm, surface modified silica particles. During this study it was shown that both the colloidal suspension conductivity and the applied electric field drive the penetration into the porous film. FEG-SEM observations showed that large (130-nm diameter), linear pores of 10 μm in length can be completely filled in 1 min. These results attest that porous anodic films can be efficiently filled with nanoparticles by EPD despite the presence of the barrier layer

The one year fate of iron oxide coated gold nanoparticles in mice

Safe implementation of nanotechnology and nanomedicine requires an in-depth understanding of the life cycle of nanoparticles in the body. Here, we investigate the long-term fate of gold/iron oxide heterostructures after intravenous injection in mice. We show these heterostructures degrade in vivo and that the magnetic and optical properties change during the degradation process. These particles eventually eliminate from the body. The comparison of two different coating shells for heterostructures, amphiphilic polymer or polyethylene glycol, reveals the long lasting impact of initial surface properties on the nanocrystal degradability and on the kinetics of elimination of magnetic iron and gold from liver and spleen. Modulation of nanoparticles reactivity to the biological environment by the choice of materials and surface functionalization may provide new directions in the design of multifunctional nanomedicines with predictable fate

Biomarkers of resistance to immune checkpoint inhibitors in non-small-cell lung cancer: myth or reality?

Immune checkpoint inhibitors represent a major therapeutic advance in non-small-cell lung cancer with several approved anti-programmed death-1 and anti-programmed death-L1 immunotherapies. A majority of patients however, will not respond to immune checkpoint inhibitors and display primary resistance while a subset of initially responsive patients will present secondary resistance. Thus, there is a crucial need for biomarkers to enable better prediction and diagnosis, and to overcome such resistance. Along with improvement in the understanding of immune escape, new biomarkers are being developed, including large scale proteomic, genomic and transcriptomic approaches in tumor and blood samples. We review the novel biomarkers that have been investigated in non-small-cell lung cancer and discuss how they can rationalize therapeutic strategies

More than local adaptation: high diversity of response to seawater acidification in seven coral species from the same assemblage in French Polynesia

International audienceAbstract Responses of corals to seawater acidification have been extensively studied. Sensitivity varies widely between species, highlighting the need to avoid extrapolation from one to another to get an accurate understanding of coral community responses. We tested the responses of seven coral species ( Acropora cytherea , Acropora hyacinthus , Acropora pulchra , Leptastrea pruinosa , Montipora grisea , Pavona cactus , Pocillopora verrucosa ) from the Mo'orea lagoon to a 48-day exposure to three pH scenarios (pH 7.95, 7.7 and 7.3). Tissue necrosis, mortality, growth rates, photophysiological performances and colour index were recorded. Few significant differences were noted between pH 7.95 and 7.7, but species-specific responses were observed at pH 7.3. While our data do not allow identification of the mechanisms behind this diversity in response between species inhabiting the same environment, it can exclude several hypotheses such as local adaptation, skeletal type, corallum morphology or calcification rate as sole factors determining coral sensitivity to pH

Seawater carbonate chemistry and tissue necrosis, photosynthetic efficiency and colour index of seven coral species

Responses of corals to seawater acidification have been extensively studied. Sensitivity varies widely between species, highlighting the need to avoid extrapolation from one to another to get an accurate understanding of coral community responses. We tested the responses of seven coral species (Acropora cytherea, Acropora hyacinthus, Acropora pulchra, Leptastrea pruinosa, Montipora grisea, Pavona cactus, Pocillopora verrucosa) from the Mo'orea lagoon to a 48-day exposure to three pH scenarios (pH 7.95, 7.7 and 7.3). Tissue necrosis, mortality, growth rates, photophysiological performances and colour index were recorded. Few significant differences were noted between pH 7.95 and 7.7, but species-specific responses were observed at pH 7.3. While our data do not allow identification of the mechanisms behind this diversity in response between species inhabiting the same environment, it can exclude several hypotheses such as local adaptation, skeletal type, corallum morphology or calcification rate as sole factors determining coral sensitivity to pH

Cancer-Associated Thrombosis on Bevacizumab: Risk of Recurrence and Bleeding When Bevacizumab Is Stopped or Continued

International audienceCancer-associated thrombosis (CAT) is a common complication during cancer, with complex management due to an increased risk of both recurrence and bleeding. Bevacizumab is an effective anti-angiogenic treatment but increases the risk of bleeding and potentially the risk of venous thromboembolism (VTE). The aim of this study was to evaluate the efficacy and safety of anticoagulant therapy in patients with CAT receiving bevacizumab, according to the continuation or discontinuation of bevacizumab. In a retrospective multicenter study, patients receiving anticoagulant for CAT occurring under bevacizumab therapy were included. The primary endpoint combined recurrent VTE and/or major or clinically relevant non-major bleeding. Among the 162 patients included, bevacizumab was discontinued in 70 (43.2%) patients and continued in 92 (56.8%) patients. After a median follow-up of 318 days, 21 (30.0%) patients in the discontinuation group experienced VTE recurrence or major or clinically relevant non-major bleeding, compared to 27 (29.3%) in the continuation group. The analysis of survival following the first event showed no significant difference between the groups in uni- or multivariate analysis (p = 0.19). The primary endpoint was not influenced by the duration of bevacizumab exposure. These results suggest that the efficacy and safety of anticoagulant therapy in patients with CAT receiving bevacizumab is not modified regardless of whether bevacizumab is continued or discontinued

Longitudinal Study of Advanced Non-Small Cell Lung Cancer with Initial Durable Clinical Benefit to Immunotherapy: Strategies for Anti-PD-1/PD-L1 Continuation beyond Progression

Background and aim: A better understanding of resistance to checkpoint inhibitors is essential to define subsequent treatments in advanced non-small cell lung cancer. By characterizing clinical and radiological features of progression after anti-programmed death-1/programmed death ligand-1 (anti-PD-1/PD-L1), we aimed to define therapeutic strategies in patients with initial durable clinical benefit. Patients and methods: This monocentric, retrospective study included patients who presented progressive disease (PD) according to RECIST 1.1 criteria after anti-PD-1/PD-L1 monotherapy. Patients were classified into two groups, “primary resistance” and “Progressive Disease (PD) after Durable Clinical Benefit (DCB)”, according to the Society of Immunotherapy of Cancer classification. We compared the post-progression survival (PPS) of both groups and analyzed the patterns of progression. An exploratory analysis was performed using the tumor growth rate (TGR) to assess the global growth kinetics of cancer and the persistent benefit of immunotherapy beyond PD after DCB. Results: A total of 148 patients were included; 105 of them presented “primary resistance” and 43 “PD after DCB”. The median PPS was 5.2 months (95% CI: 2.6–6.5) for primary resistance (p < 0.0001) vs. 21.3 months (95% CI: 18.5–36.3) for “PD after DCB”, and the multivariable hazard ratio was 0.14 (95% CI: 0.07–0.30). The oligoprogression pattern was frequent in the “PD after DCB” group (76.7%) and occurred mostly in pre-existing lesions (72.1%). TGR deceleration suggested a persistent benefit of PD-1/PD-L1 blockade in 44.2% of cases. Conclusions: PD after DCB is an independent factor of longer post-progression survival with specific patterns that prompt to contemplate loco-regional treatments. TGR is a promising tool to assess the residual benefit of immunotherapy and justify the continuation of immunotherapy in addition to radiotherapy or surgery

Design of Covalently Functionalized Carbon Nanotubes Filled with Metal Oxide Nanoparticles for Imaging, Therapy, and Magnetic Manipulation

Nanocomposites combining multiple functionalities in one single nano-object hold great promise for biomedical applications. In this work, carbon nanotubes (CNTs) were filled with ferrite nanoparticles (NPs) to develop the magnetic manipulation of the nanotubes and their theranostic applications. The challenges were both the filling of CNTs with a high amount of magnetic NPs and their functionalization to form biocompatible water suspensions. We propose here a filling process using CNTs as nanoreactors for high-yield <i>in situ</i> growth of ferrite NPs into the inner carbon cavity. At first, NPs were formed inside the nanotubes by thermal decomposition of an iron stearate precursor. A second filling step was then performed with iron or cobalt stearate precursors to enhance the encapsulation yield and block the formed NPs inside the tubes. Water suspensions were then obtained by addition of amino groups <i>via</i> the covalent functionalization of the external surface of the nanotubes. Microstructural and magnetic characterizations confirmed the confinement of NPs into the anisotropic structure of CNTs making them suitable for magnetic manipulations and MRI detection. Interactions of highly water-dispersible CNTs with tumor cells could be modulated by magnetic fields without toxicity, allowing control of their orientation within the cell and inducing submicron magnetic stirring. The magnetic properties were also used to quantify CNTs cellular uptake by measuring the cell magnetophoretic mobility. Finally, the photothermal ablation of tumor cells could be enhanced by magnetic stimulus, harnessing the hybrid properties of NP loaded-CNTs

Design of Covalently Functionalized Carbon Nanotubes Filled with Metal Oxide Nanoparticles for Imaging, Therapy, and Magnetic Manipulation

Nanocomposites combining multiple functionalities in one single nano-object hold great promise for biomedical applications. In this work, carbon nanotubes (CNTs) were filled with ferrite nanoparticles (NPs) to develop the magnetic manipulation of the nanotubes and their theranostic applications. The challenges were both the filling of CNTs with a high amount of magnetic NPs and their functionalization to form biocompatible water suspensions. We propose here a filling process using CNTs as nanoreactors for high-yield in situ growth of ferrite NPs into the inner carbon cavity. At first, NPs were formed inside the nanotubes by thermal decomposition of an iron stearate precursor. A second filling step was then performed with iron or cobalt stearate precursors to enhance the encapsulation yield and block the formed NPs inside the tubes. Water suspensions were then obtained by addition of amino groups via the covalent functionalization of the external surface of the nanotubes. Microstructural and magnetic characterizations confirmed the confinement of NPs into the anisotropic structure of CNTs making them suitable for magnetic manipulations and MRI detection. Interactions of highly water-dispersible CNTs with tumor cells could be modulated by magnetic fields without toxicity, allowing control of their orientation within the cell and inducing submicron magnetic stirring. The magnetic properties were also used to quantify CNTs cellular uptake by measuring the cell magnetophoretic mobility. Finally, the photothermal ablation of tumor cells could be enhanced by magnetic stimulus, harnessing the hybrid properties of NP loaded-CNTs