Self-assembling nanoparticles encapsulating zoledronic acid inhibit mesenchymal stromal cells differentiation, migration and secretion of proangiogenic factors and their interactions with prostate cancer cells

摘要: // Cinzia Borghese 1, * , Naike Casagrande Eliana Pivetta 1 Alfonso Colombatti Mariarosaria Boccellino 2, 3 Evzen Amler 4, 5 Nicola Normanno 6 Michele Caraglia Giuseppe De Rosa 7 and Donatella Aldinucci Molecular Oncology Unit, Centro di Riferimento Oncologico, IRCCS-National Cancer Institute, Aviano, PN, Italy 2 Department of Biochemistry, Biophysics General Pathology, Second University Naples, Sbarro Institute for Research Medicine, Center Biotechnology, College Science Technology, Temple University, Philadelphia, PA, USA 4 Indoor Environmental Quality, Energy Efficient Buildings, Czech Technical in Prague, Bustěhrad, Republic Laboratory Tissue Engineering, Experimental Academy Sciences, Cell Biology & Biotherapy Istituto Nazionale Tumori “Fondazione G Pascale”-IRCCS, Pharmacy, Federico II These authors have contributed equally to this work Correspondence to: Aldinucci, email: daldinucci@cro.it Keywords: zoledronic acid, self-assembling nanoparticles, mesenchymal stromal cells, prostate cancer, tumor microenvironment Received: January 21, 2017     Accepted: March 22, Published: April 19, 2017 ABSTRACT Zoledronic Acid (ZA) rapidly concentrates into the bone reduces skeletal-related events pain metastatic cancer (PCa), but exerts only a limited or absent impact as anti-cancer activity. Recently, we developed nanoparticles (NPS) encapsulating acid (NZ) that allowed higher intratumor delivery drug compared with free vivo models PCa. Increasing evidence suggests Bone Marrow (BM) Mesenchymal cells (BM-MSCs) are recruited stroma developing tumors where they contribute progression by enhancing growth metastasis. We demonstrated treatment NZ decreased migration differentiation adipocytes osteoblasts MSCs inhibited osteoclastogenesis. Treatment reduced capability promote clonogenic cell lines PC3 DU145. The levels Interleukin-6 pro-angiogenic factors VEGF FGF-2 were significantly MSC-CM derived from treated NZ, CCL5 secretion was almost totally abolished. Moreover, supernatants leading tumor-educated (TE-MSCs), increased IL-6, CCL5, their increase growth. cytokine pro-tumorigenic effects also TE-MSCS. In conclusion, demonstrating is capable inhibit cross talk between PCa, study provides novel insight explain powerful anticancer activity on