Article abstract
Nature Materials
Published online: 8 November 2009 | doi:10.1038/nmat2569
Self-assembling chimeric polypeptide–doxorubicin conjugate nanoparticles that abolish tumours after a single injection
J. Andrew MacKay1,3, Mingnan Chen2,3, Jonathan R. McDaniel2, Wenge Liu2, Andrew J. Simnick2 & Ashutosh Chilkoti2
Abstract
New strategies to self-assemble biocompatible materials into nanoscale, drug-loaded packages with improved therapeutic efficacy are needed for nanomedicine. To address this need, we developed artificial recombinant chimeric polypeptides (CPs) that spontaneously self-assemble into sub-100-nm-sized, near-monodisperse nanoparticles on conjugation of diverse hydrophobic molecules, including chemotherapeutics. These CPs consist of a biodegradable polypeptide that is attached to a short Cys-rich segment. Covalent modification of the Cys residues with a structurally diverse set of hydrophobic small molecules, including chemotherapeutics, leads to spontaneous formation of nanoparticles over a range of CP compositions and molecular weights. When used to deliver chemotherapeutics to a murine cancer model, CP nanoparticles have a fourfold higher maximum tolerated dose than free drug, and induce nearly complete tumour regression after a single dose. This simple strategy can promote co-assembly of drugs, imaging agents and targeting moieties into multifunctional nanomedicines.
- Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, 90033-9121, USA
- Department of Biomedical Engineering, Duke University, Durham, North Carolina, 27708-0281, USA
- These authors contributed equally to this work
Correspondence to: Ashutosh Chilkoti2 e-mail: chilkoti@duke.edu
