A Nanoparticle for Tumor Targeted Delivery of Oligomers
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.
Key wordsTumor delivery streptavidin nanoparticle antisense
This work was supported in part by the Office of Science (BER), U.S. Department of Energy (grant DE-FG02-03ER63602); the National Institutes of Health (grant R01CA94994 and R21CA129591); and congressionally directed Medical Research Programs (grant W81XWH-06-1-0649).