Labeling and exocytosis of secretory compartments in RBL mastocytes by polystyrene and mesoporous silica nanoparticles

Maneerat Ekkapongpisit1,*, Antonino Giovia1,*, Giuseppina Nicotra1, Matteo Ozzano1, Giuseppe Caputo2,3, Ciro Isidoro1 1Laboratory of Molecular Pathology and Nanobioimaging, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara, Italy; 2Department of Chemistry, University of Turin, Turin, 3Cyanine Technology SpA, Torino, Italy *These authors contributed equally to this workBackground: For a safe ‘in vivo’ biomedical utilization of nanoparticles, it is essential to assess not only biocompatibility, but also the potential to trigger unwanted side effects at both cellular and tissue levels. Mastocytes (cells having secretory granules containing cytokines, vasoactive amine, and proteases) play a pivotal role in the immune and inflammatory responses against exogenous toxins. Mastocytes are also recruited in the tumor stroma and are involved in tumor vascularization and growth.Aim and methods: In this work, mastocyte-like rat basophilic leukemia (RBL) cells were used to investigate whether carboxyl-modified 30 nm polystyrene (PS) nanoparticles (NPs) and naked mesoporous silica (MPS) 10 nm NPs are able to label the secretory inflammatory granules, and possibly induce exocytosis of these granules. Uptake, cellular retention and localization of fluorescent NPs were analyzed by cytofluorometry and microscope imaging.Results: Our findings were that: (1) secretory granules of mastocytes are accessible by NPs via endocytosis; (2) PS and MPS silica NPs label two distinct subpopulations of inflammatory granules in RBL mastocytes; and (3) PS NPs induce calcium-dependent exocytosis of inflammatory granules.Conclusion: These findings highlight the value of NPs for live imaging of inflammatory processes, and also have important implications for the clinical use of PS-based NPs, due to their potential to trigger the unwanted activation of mastocytes.Keywords: secretory lysosomes, inflammation, nanoparticles, vesicular traffi

Epigenetic Control of Autophagy by MicroRNAs in Ovarian Cancer

Autophagy is a lysosomal-driven catabolic process that contributes to the preservation of cell homeostasis through the regular elimination of cellular damaged, aged, and redundant molecules and organelles. Autophagy plays dual opposite roles in cancer: on one hand it prevents carcinogenesis; on the other hand it confers an advantage to cancer cells to survive under prohibitive conditions. Autophagy has been implicated in ovarian cancer aggressiveness and in ovarian cancer cell chemoresistance and dormancy. Small noncoding microRNAs (miRNAs) regulate gene expression at posttranscriptional level, thus playing an important role in many aspects of cell pathophysiology, including cancerogenesis and cancer progression. Certain miRNAs have recently emerged as important epigenetic modulators of autophagy in cancer cells. The mRNA of several autophagy-related genes contains, in fact, the target sequence for miRNAs belonging to different families, with either oncosuppressive or oncogenic activities. MiRNA profiling studies have identified some miRNAs aberrantly expressed in ovarian cancer tissues that can impact autophagy. In addition, plasma and stroma cell-derived miRNAs in tumour-bearing patients can regulate the expression of relevant autophagy genes in cancer cells. The present review focuses on the potential implications of miRNAs regulating autophagy in ovarian cancer pathogenesis and progression