Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre‐clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC) is reported to improve oxygen diffusion through the tumor environment. Early pharmacokinetic analysis of the clinical trial of this molecule performed on 37 patients orient to define the optimal fixed dosage to use in a triple‐negative breast cancer model to validate the therapeutic combination of radiation therapy and NP TSC. Notably, it is reported that this formulation is non‐toxic in both humans and mice at the defined fixed concentration, provides a normalization of the tumor vasculature within 72 h window after systemic injection, leads to a transient increase (50% improvement) in the tumor oxygenation, and significantly improves the efficacy of both mono‐fractionated and fractionated radiation therapy treatment. Together, these findings support the introduction of a first‐in‐class therapeutic construct capable of tumor‐specific reoxygenation without associated toxicities

Cancer drug resistance: rationale for drug delivery systems and targeted inhibition of HSP90 family proteins

International audienc

Cancer drug resistance: rationale for drug delivery systems and targeted inhibition of HSP90 family proteins

Nanocarriers have been developed in order to protect drugs or to improve drugs efficiency by reaching the damaged tissue and avoiding systemic and local toxicity. By using HSP90 inhibitors, some cancer drug resistances have been overcome and the loading into nanocarriers of such drugs has shown an increase of their activities. This review will present some advantages of HSP90 inhibitors to treat resistant tumors; especially those targeting the mitochondrial protein TRAP1. We will also focus on the targeting of the primary tumors, cancer stem cells and metastatic cells

Anti-BCMA Immuno-NanoPET Radiotracers for Improved Detection of Multiple Myeloma

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Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma

International audienceDespite combined treatments, glioblastoma outcome remains poor with frequent local recurrences, indicating that a more efficient and local therapy is needed. In this way, vascular-targeted photodynamic therapy (VTP) is a promising complementary approach to improve tumor eradication1 by destroying its neovessels2. In this study, we designed a polysiloxane-based nanoparticle (NP) combining a magnetic resonance imaging (MRI) contrast agent, a photosensitizer (PS) and a new ligand peptide motif (KDKPPR) targeting neuropilin-1 (NRP-1)3,4, a receptor overexpressed by angiogenic endothelial cells of the tumor vasculature. This structure achieves the detection of the tumor tissue and its proliferating part by MRI analysis, followed by its treatment by VTP. The photophysical properties of the PS and the peptide affinity for NRP-1 recombinant protein were preserved after the functionalization of NPs. Cellular uptake of NPs by human umbilical vein endothelial cells (HUVEC) was increased twice compared to NPs without the KDKPPR peptide moiety or conjugated with a scramble peptide. NPs induced no cytotoxicity without light exposure but conferred a photocytotoxic effect to cells after photodynamic therapy (PDT)5. In vivo, complementary approaches were investigated, combining non-invasive imaging by magnetic resonance or by fluorescence and a tissue assay by ICP-MS to determine gadolinium concentrations, revealing renal and hepatic eliminations. The tumor selectivity of the NPs compared to the healthy brain parenchyma was validated by MRI data. The in vivo selectivity, evaluated using a skinfold chamber model in mice, confirms that the functionalized NPs with KDKPPR peptide moiety were localized in the tumor vessel wall, validating this vascular targeting strategy

Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma

International audienceDespite combined treatments, glioblastoma outcome remains poor with frequent local recurrences, indicating that a more efficient and local therapy is needed. In this way, vascular-targeted photodynamic therapy (VTP) could help tumor eradication by destroying its neovessels. In this study, we designed a polysiloxane-based nanoparticle (NP) combining a magnetic resonance imaging (MRI) contrast agent, a photosensitizer (PS) and a new ligand peptide motif (KDKPPR) targeting neuropilin-1 (NRP-1), a receptor overexpressed by angiogenic endothelial cells of the tumor vasculature. This structure achieves the detection of the tumor tissue and its proliferating part by MRI analysis, followed by its treatment by VTP. The photophysical properties of the PS and the peptide affinity for NRP-1 recombinant protein were preserved after the functionalization of NPs. Cellular uptake of NPs by human umbilical vein endothelial cells (HUVEC) was increased twice compared to NPs without the KDKPPR peptide moiety or conjugated with a scramble peptide. NPs induced no cytotoxicity without light exposure but conferred a photocytotoxic effect to cells after photodynamic therapy (PDT). The in vivo selectivity, evaluated using a skinfold chamber model in mice, confirms that the functionalized NPs with KDKPPR peptide moiety were localized in the tumor vessel wall

Farming intensity indirectly reduces crop yield through negative effects on agrobiodiversity and key ecological functions

International audienceFarming intensity and landscape heterogeneity influence agrobiodiversity and associated ecological functions. The relative contributions of these agroecosystem components to agricultural production remain unclear because of inter-relations and weather-dependant variations. Using a structural equation modelling approach, we estimated direct and indirect contributions of farming intensity (soil management, pesticide use and fertilisation) and landscape heterogeneity (of semi-natural covers and crop mosaic) to cereal crop production, in 54 fields (mostly wheat), in two years (24 and 30 fields). Indirect effects were evaluated through agrobiodiversity (carabid and plant communities) and ecological functions (pollination and pest control). In 2016, farming intensity had the largest direct positive effect on cereal crop yield, followed by agrobiodiversity (74% of the farming intensity impact) and ecological functions. However, the direct benefits of farming intensity were halved due to negative indirect effects, as farming intensity negatively affected within-field biodiversity and ecological functions. Overall, agrobiodiversity and farming intensity had equal net contributions to cereal crop yields, while heterogeneity of the crop mosaic enhanced biodiversity. In 2017, neither higher farming intensity nor agrobiodiversity and ecological functions could lift cereal production, which suffered from unfavourable meteorological conditions. Semi-natural habitats supported agrobiodiversity. Our study suggests that a reduction of farming intensity combined with higher heterogeneity of crop mosaic can enhance the benefits of ecological functions towards crop production. Semi-natural covers seem to play an essential role in the face of climatic events, by supporting agrobiodiversity and the potential resilience of the agroecosystem functioning

Agro-environmental indicators. New IACS VISION in ACTION – NIVA

Context and objectives: Agricultural activities have a strong impact on the environment ; UC1b has developed a set of indicators based on existing scientific methods and on data widely available in Europe (IACS, Sentinel-2 images, topographic data) ; Computation tools are open-source and available on the NIVA GitLab : gitlab.com/nivaeu. These indicators may contribute to assess some of the new CAP objectives and some Sustainable Development Goals Carbon indicator: annual CO 2 flux due to crop vegetation cycle . CO 2 flux takes into the account the CO 2 emitted in the atmosphere (plants and soil respiration) and the CO 2 stored by plants due to photosynthesis. The computation of CO 2 flux is based on an empirical method: for main crops, annual CO2 flux depends on the number of days with active vegetation. This number of days is estimated from NDVI temporal series (from Sentinel-2 images). The computation tool has been tested on various areas in Europe (France, Denmark, Netherlands, Spain) NIVA H2020 PROJECT www.niva4cap.eu Spanish results in Castile and Leo

Agro-environmental indicators. New IACS VISION in ACTION – NIVA

International audienceContext and objectives: Agricultural activities have a strong impact on the environment ; UC1b has developed a set of indicators based on existing scientific methods and on data widely available in Europe (IACS, Sentinel-2 images, topographic data) ; Computation tools are open-source and available on the NIVA GitLab : gitlab.com/nivaeu. These indicators may contribute to assess some of the new CAP objectives and some Sustainable Development Goals Carbon indicator: annual CO 2 flux due to crop vegetation cycle . CO 2 flux takes into the account the CO 2 emitted in the atmosphere (plants and soil respiration) and the CO 2 stored by plants due to photosynthesis. The computation of CO 2 flux is based on an empirical method: for main crops, annual CO2 flux depends on the number of days with active vegetation. This number of days is estimated from NDVI temporal series (from Sentinel-2 images). The computation tool has been tested on various areas in Europe (France, Denmark, Netherlands, Spain) NIVA H2020 PROJECT www.niva4cap.eu Spanish results in Castile and Leo