Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune stimulatory cytokine and natural endotoxin that can induce necrosis and regression in solid tumors. However, systemic administration of TNF-α is not feasible due to its short half-life and acute toxicity, preventing its widespread use in cancer treatment. Dendritic mesoporous silica nanoparticles (DMSN) are used coated with a pH-responsive block copolymer gate system combining charged hyperbranched polyethylenimine and nonionic hydrophilic polyethylenglycol to encapsulate TNF-α and deliver it into various cancer cell lines and dendritic cells. Half-maximal effective concentration (EC ) for loaded TNF-α is reduced by more than two orders of magnitude. Particle stability and premature cargo release are assessed with enzyme-linked immunosorbent assay. TNF-α-loaded particles are stable for up to 5 d in medium. Tumor cells are grown in vitro as 3D fluorescent ubiquitination-based cell cycle indicator spheroids that mimic in vivo tumor architecture and microenvironment, allowing real-time cell cycle imaging. DMSN penetrate these spheroids, release TNF-α from its pores, preferentially affect cells in S/G2/M phase, and induce cell death in a time- and dose-dependent manner. In conclusion, DMSN encapsulation is demonstrated, which is a promising approach to enhance delivery and efficacy of antitumor drugs, while minimizing adverse side effects.

Background Ceylon cinnamon has been shown to possess anti‐inflammatory properties in many diseases including allergic inflammation. Objective The aim of this study was to analyse in more detail the effects of cinnamon extract (CE) and its major compounds p‐cymene and trans‐cinnamaldehyde (CA) on allergen‐specific immune responses in vitro and in vivo. Methods Therefore, monocyte‐derived mature dendritic cells (DC) from grass or birch pollen allergic donors were pulsed with the respective allergen in the presence or absence of CE, p‐cymene, CA or the solvent ethanol and co‐cultured with autologous CD4+ T cells. Furthermore, basophil activation test was performed with or without CE or ethanol treatment. For the in vivo experiments, BALB/c mice were immunized with ovalbumin (OVA) and orally treated with CE or ethanol. Results Addition of CE, p‐cymene or CA, but not ethanol significantly inhibited DC maturation and subsequent allergen‐specific T cell proliferation as well as Th1 and Th2 cytokine production. Sulphidoleukotriene release and CD63 expression by basophils were also significantly diminished after addition of CE. In vivo, treatment of OVA‐sensitized mice with CE led to a significant shift from OVA‐specific IgE towards IgG2a production and to a strong inhibition of OVA‐specific proliferation. Moreover, airway inflammation as well as anaphylaxis after intranasal or systemic allergen challenge was significantly reduced in CE‐treated mice. Furthermore, topical application of CE prevented calcipotriol‐induced atopic dermatitis‐like inflammation in these mice. Conclusions and Clinical Relevance Taken together, our data indicate that the anti‐inflammatory effect of cinnamon might be exploited for treatment of allergic inflammation, which needs to be further investigated.

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In article number 1700012, Helmut Jonuleit and co-workers utilize dendritic mesoporous silica nanoparticles for drug delivery to increase the efficacy of anti-tumor drug TNF-a, while decreasing its side-effects.