title: Bioresponsive antisense DNA gold nanobeacons as a hybrid in vivo theranostics platform for the inhibition of cancer cells and metastasis.
abstract: Gold nanobeacons can be used as a powerful tool for cancer theranostics. Here, we proposed a nanomaterial platform based on gold nanobeacons to detect, target and inhibit the expression of a mutant Kras gene in an in vivo murine gastric cancer model. The conjugation of fluorescently-labeled antisense DNA hairpin oligonucleotides to the surface of gold nanoparticles enables using their localized surface plasmon resonance properties to directly track the delivery to the primary gastric tumor and to lung metastatic sites. The fluorescently labeled nanobeacons reports on the interaction with the target as the fluorescent Cy3 signal is quenched by the gold nanoparticle and only emit light following conjugation to the Kras target owing to reorganization and opening of the nanobeacons, thus increasing the distance between the dye and the quencher. The systemic administration of the anti-Kras nanobeacons resulted in approximately 60% tumor size reduction and a 90% reduction in tumor vascularization. More important, the inhibition of the Kras gene expression in gastric tumors prevents the occurrence of metastasis to lung (80% reduction), increasing mice survival in more than 85%. Our developed platform can be easily adjusted to hybridize with any specific target and provide facile diagnosis and treatment for neoplastic diseases.
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Lab. of Thin Film and Microfabrication Technology of Ministry of Education, Department of instrument science and engineering, School of Electronic Information and Electrical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, P.R.China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Bao
authors.affiliation: 1] Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts, USA [2] School of Engineering and Materials Science, Queen Mary University of London, London, UK.
authors.forename: João
authors.initials: J
authors.lastname: Conde
authors.affiliation: School of Food Science and Environmental Health, College of Sciences and Health, Dublin Institute of Technology, Cathal Brugha Street, Dublin, Ireland.
authors.forename: James
authors.initials: J
authors.lastname: Curtin
authors.affiliation: 1] Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts, USA [2] Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Artzi
authors.affiliation: Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin, Ireland.
authors.forename: Furong
authors.initials: F
authors.lastname: Tian
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Lab. of Thin Film and Microfabrication Technology of Ministry of Education, Department of instrument science and engineering, School of Electronic Information and Electrical Engineering, National Center for Translational Medicine, Shanghai Jiao Tong University, P.R.China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016373:DNA, Antisense / Q000008:administration & dosage / Q000737:chemistry; D004195:Disease Models, Animal; D006046:Gold / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D017550:Spectroscopy, Fourier Transform Infrared; D000068936:Theranostic Nanomedicine; D023041:Xenograft Model Antitumor Assays
chemical_list: D016373:DNA, Antisense; D006046:Gold; D016283:Proto-Oncogene Proteins p21(ras)