@article {3136458,
	title = {Identification of Dormancy-Associated MicroRNAs for the Design of Osteosarcoma-Targeted Dendritic Polyglycerol Nanopolyplexes},
	journal = {ACS Nano},
	volume = {10},
	year = {2016},
	month = {2016 Feb 23},
	pages = {2028-45},
	abstract = {The presence of dormant, microscopic cancerous lesions poses a major obstacle for the treatment of metastatic and recurrent cancers. While it is well-established that microRNAs play a major role in tumorigenesis, their involvement in tumor dormancy has yet to be fully elucidated. We established and comprehensively characterized pairs of dormant and fast-growing human osteosarcoma models. Using these pairs of mouse tumor models, we identified three novel regulators of osteosarcoma dormancy: miR-34a, miR-93, and miR-200c. This report shows that loss of these microRNAs occurs during the switch from dormant avascular into fast-growing angiogenic phenotype. We validated their downregulation in patients{\textquoteright} tumor samples compared to normal bone, making them attractive candidates for osteosarcoma therapy. Successful delivery of miRNAs is a challenge; hence, we synthesized an aminated polyglycerol dendritic nanocarrier, dPG-NH2, and designed dPG-NH2-microRNA polyplexes to target cancer. Reconstitution of these microRNAs using dPG-NH2 polyplexes into Saos-2 and MG-63 cells, which generate fast-growing osteosarcomas, reduced the levels of their target genes, MET proto-oncogene, hypoxia-inducible factor 1α, and moesin, critical to cancer angiogenesis and cancer cells{\textquoteright} migration. We further demonstrate that these microRNAs attenuate the angiogenic capabilities of fast-growing osteosarcomas in vitro and in vivo. Treatment with each of these microRNAs using dPG-NH2 significantly prolonged the dormancy period of fast-growing osteosarcomas in vivo. Taken together, these findings suggest that nanocarrier-mediated delivery of microRNAs involved in osteosarcoma tumor-host interactions can induce a dormant-like state.},
	keywords = {Animals, Antineoplastic Agents, Cell Line, Tumor, Drug Carriers, Drug discovery, glycerol, Humans, Mice, Mice, SCID, MicroRNAs, Nanomedicine, Nanostructures, Osteosarcoma, Polymers, Proto-Oncogene Mas},
	issn = {1936-086X},
	doi = {10.1021/acsnano.5b06189},
	author = {Galia Tiram and Segal, Ehud and Adva Krivitsky and Shreberk-Hassidim, Rony and Ferber, Shiran and Ofek, Paula and Udagawa, Taturo and Edry, Liat and Shomron, Noam and Roniger, Maayan and Kerem, Batsheva and Yuval Shaked and Aviel-Ronen, Sarit and Barshack, Iris and Calder{\'o}n, Marcelo and Haag, Rainer and Ronit Satchi-Fainaro}
}
