1. Highly stable, ligand-clustered 'patchy' micelle nanocarriers for systemic tumor targeting
- Author
-
Jung Ah Lee, Paula T. Hammond, Zhiyong Poon, Richard J. Prevost, Shenwen Huang, Massachusetts Institute of Technology. Department of Chemical Engineering, Poon, Zhiyong, Lee, Jung Ah, Huang, Shenwen, Prevost, Richard J., and Hammond, Paula T.
- Subjects
Materials science ,Paclitaxel ,Biomedical Engineering ,Mice, Nude ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Pharmacology ,Ligands ,Micelle ,Article ,Mice ,chemistry.chemical_compound ,Drug Stability ,In vivo ,Cell Line, Tumor ,Dendrimer ,Animals ,Humans ,General Materials Science ,Micelles ,Drug Carriers ,Mice, Inbred BALB C ,Carcinoma ,Antineoplastic Agents, Phytogenic ,Xenograft Model Antitumor Assays ,Nanomedicine ,chemistry ,Targeted drug delivery ,Injections, Intravenous ,Biophysics ,Nanoparticles ,Molecular Medicine ,Nanocarriers ,Drug carrier - Abstract
A novel linear-dendritic block copolymer has been synthesized and evaluated for targeted delivery. The use of the dendron as the micellar exterior block in this architecture allows the presentation of a relatively small quantity of ligands in clusters for enhanced targeting, thus maintaining a long circulation time of these “patchy” micelles. The polypeptide linear hydrophobic block drives formation of micelles that carry core-loaded drugs, and their unique design gives them extremely high stability in vivo. We have found that these systems lead to extended time periods of increased accumulation in the tumor (up to 5 days) compared with nontargeted vehicles. We also demonstrate a fourfold increase in efficacy of paclitaxel when delivered in the targeted nanoparticle systems, while significantly decreasing in vivo toxicity of the chemotherapy treatment., National Institute for Biomedical Imaging and Bioengineering (U.S.), National Cancer Institute (U.S.) (R01EB008082-01A2)
- Published
- 2011