RESUMEN
Calcium nanoparticles have been investigated for applications, such as drug and gene delivery. Additionally, Ca2+ serves as a crucial second messenger in the activation of immune cells. However, few studies have systematically studied the effects of calcium nanoparticles on the calcium levels and functions within immune cells. In this study, we explore the potential of calcium nanoparticles as a vehicle to deliver calcium into the cytosol of dendritic cells (DCs) and influence their functions. We synthesized calcium hydroxide nanoparticles, coated them with a layer of silica to prevent rapid degradation, and further conjugated them with anti-CD205 antibodies to achieve targeted delivery to DCs. Our results indicate that these nanoparticles can efficiently enter DCs and release calcium ions in a controlled manner. This elevation in cytosolic calcium activates both the NFAT and NF-κB pathways, in turn promoting the expression of costimulatory molecules, antigen-presenting molecules, and pro-inflammatory cytokines. In mouse tumor models, the calcium nanoparticles enhanced the antitumor immune response and augmented the efficacy of both radiotherapy and chemotherapy without introducing additional toxicity. Our study introduces a safe nanoparticle immunomodulator with potential widespread applications in cancer therapy.
Asunto(s)
Calcio , Nanopartículas , Animales , Ratones , Calcio/metabolismo , Citosol/metabolismo , Citocinas/metabolismo , Células Dendríticas , Inmunoterapia/métodosRESUMEN
Pesticide use in peri-urban areas affects the urban environment and public health, and reducing the use may present food security issues for urban dwellers. In this study, we explore how a municipality-adopted goal of a 20% reduction in pesticide use could be achieved, along with local food security and environmental implications, for Shanghai located in the densely populated East China. A regional Shanghai Agricultural Sector Model incorporating district- and technology-varying crop budgets, was developed to simulate the effects of pesticide reduction policy. Here we find that achieving the reduction goal had the largest implications in districts with high pesticide use totals and intensities, potentially reducing pesticide non-point source pollution in the Yangtze River Estuary and Dianshan Lake; the production levels of rice and leafy vegetables would be most affected; and adopting machinery that allows more precise pesticide application modulates these results. Moreover, imposing the requirements at the district-level caused more severe local food security concerns, and less environmental benefits. Furthermore, a closed Shanghai's agricultural economy would substantially enlarge the regional heterogeneity in the above-mentioned outcomes. Exploring the effects of a quantity control policy on current-use pesticides at different aggregation levels has important implications for regulating the use of agrochemicals.