Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • MacKay, JA; Chen, M; McDaniel, JR; Liu, W; Simnick, AJ; Chilkoti, A

Published Date

  • December 2009

Published In

Volume / Issue

  • 8 / 12

Start / End Page

  • 993 - 999

PubMed ID

  • 19898461

Pubmed Central ID

  • 19898461

International Standard Serial Number (ISSN)

  • 1476-1122

Digital Object Identifier (DOI)

  • 10.1038/nmat2569

Language

  • eng