Transitions to food democracy through multilevel governance

status: publishe

Polysaccharide-based nanocarriers targeting CD44 for lung cancer treatment

International audienc

Targeting CD44 receptor-positive lung tumors using polysaccharide-based nanocarriers: Influence of nanoparticle size and administration route

International audienceNew approaches that are more efficient and able to specifically reach lung tumors are needed. We developed new hyaluronan-based nanoparticles targeting CD44 receptors of two different sizes and compared their lung cancer cells targeting efficacy in vitro and in vivo. The nanoparticles' cellular uptake was dose-dependent, and specific to hyaluronan receptors, particularly CD44. The binding and internalization differed according to nanoparticle size. In vivo biodistribution studies in two orthotopic lung tumor models showed that intrapulmonary nebulized nanoparticles accumulated in lungs, but not in the tumor nodules. In contrast, despite a significant liver capture, intravenous injection led to a better accumulation of the nanoparticles in the lung tumors compared with the surrounding healthy lung tissues. We demonstrated that the hyaluronan-based nanoparticles size plays significant role in cellular uptake and biodistribution. Small nanoparticles showed active targeting of CD44-overexpressing tumors, suggesting that they could be used as drug-delivery system. From the Clinical Editor: Combating cancers remains an important goal in clinical medicine. In this study, the authors investigated the ability of two hyaluronan-based nanoparticles targeting CD44 receptors to home in on lung cancer cells in an in-vivo orthotropic model. The preferential uptake of smaller sized nanoparticles via intravenous route has further enhanced the existing knowledge of future drug design

Anti-tumor efficacy of hyaluronan-based nanoparticles for the co-delivery of drugs in lung cancer

International audienceCombinations of therapeutic agents could synergistically enhance the response of lung cancer cells. Co-delivery systems capable of transporting chemotherapeutics with different physicochemical properties and with the simultaneous release of drugs remain elusive. Here, we assess the ability of nanoparticles of 30-nm diameter obtained from the self-assembly of hyaluronan-based copolymer targeting CD44 receptors to encapsulate both gefitinib and vorinostat for effective combinational lung cancer treatment. Drug loading was performed by nanoprecipitation. Drug release experiments showed a slow release of both drugs after 5 days. Using two- and three-dimensional lung adenocarcinoma cell cultures, we observed that the nanoparticles were mostly found at the periphery of the CD44-expressing spheroids. These drug-loaded nanoparticles were as cytotoxic as free drugs in the two- and three-dimensional systems and toxicity was due to apoptosis induction. In mouse models, intravenous injection of hyaluronan-based nanoparticles showed a selective delivery to subcutaneous CD44-overexpressing tumors, despite a significant liver capture. In addition, the systemic toxicity of the free drugs was reduced by their co-delivery using the nanoparticles. Finally, intrapulmonary administration of drug-loaded nanoparticles, to avoid a possible hepatic toxicity due to their accumulation in the liver, showed a stronger inhibition of orthotopic lung tumor growth compared to free drugs. In conclusion, hyaluronan-based nanoparticles provide active targeting partially mediated by CD44, less-toxic drug release and improved antitumor efficiency

Transitions to food democracy through multilevel governance

International audienceFood systems in Europe are largely unjust and not sustainable. Despite substantial negative consequences for individual health, the environment and public sector health and care services, large multi-national corporations continue to benefit from the way food systems are designed—perpetuating “Lose–Lose–Lose–Win” food systems that see these large corporations benefit at the expense of health, the environment and public sector finances. Transitioning to “Win–Win–Win–Win” food systems is challenging because of the heterogeneity, complexity and unpredictable nature of food systems—one-size fits-all solutions to correct imbalances and injustices cannot exist. To address these challenges, we propose the use of heuristics—solutions that can flexibly account for different contexts, preferences and needs. Within food systems, food democracy could be a heuristic solution that provides the processes and can form the basis for driving just transitions. However, ensuring that these transition processes are fair, equitable, sustainable and constructive, requires an approach that can be used across vertical and horizontal governance spheres to ensure the voices of key stakeholders across space, time and spheres of power are accounted for. In this manuscript we outline a new Horizon project, FEAST, that aims to use multilevel governance approaches across vertical and horizontal spheres of governance to realize constructive food democracy. We envisage this as a means to inform just processes that can be used to design and implement policies, in line with food democracy, to facilitate transitions to “Win–Win–Win–Win” food systems across Europe that makes it easy for every European to eat a healthy and sustainable diet