title: A nanoparticle for tumor targeted delivery of oligomers.
abstract: The tissue-specific delivery nanoparticle consists of an antisense oligomer, a cell-penetrating peptide, and an antitumor antibody, each biotinylated and each linked via streptavidin. Within the nanoparticle, the antibody provides specific targeted delivery and binding to the target cells, the peptide improves cell membrane transport, and the antisense oligomer, through its mRNA-binding ability, provides specific retention of the radioactivity in the target cell nucleus. The use of streptavidin as linker eliminates the need for covalent conjugation without appearing to interfere with the in vitro and in vivo properties of each component. The delivery nanoparticle is under development to improve tumor targeting with unlabeled siRNAs as well as radiolabeled antisense oligomers in a variety of tumor types. The anti-HER2 Trastuzumab (Herceptin) antibody, the tat peptide, and a radiolabeled antisense oligomer against the RIα mRNA have been used in this report as an example.
authors: Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA. xinrong.liu@umassmed.edu
authors: Xinrong
authors: X
authors: Liu
authors: Yi
authors: Y
authors: Wang
authors: Donald J
authors: DJ
authors: Hnatowich
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001710:Biotin / Q000378:metabolism; D019921:Biotinylation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019809:Streptavidin / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001710:Biotin; D057846:Cell-Penetrating Peptides; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D015696:Gene Products, tat; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D019809:Streptavidin; D000068878:Trastuzumab; C508053:ERBB2 protein, human