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

Publication ,  Journal Article
MacKay, JA; Chen, M; McDaniel, JR; Liu, W; Simnick, AJ; Chilkoti, A
Published in: Nature Materials
2009

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.

Duke Scholars

Published In

Nature Materials

Publication Date

2009

Volume

8

Start / End Page

993 / 999

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Peptides
  • Particle Size
  • Neoplasms
  • Nanotechnology
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice, Inbred BALB C
  • Mice
  • Drug Delivery Systems
 

Citation

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MacKay, J. A., Chen, M., McDaniel, J. R., Liu, W., Simnick, A. J., & Chilkoti, A. (2009). Self-assembling chimeric polypeptide–doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nature Materials, 8, 993–999.
MacKay, J Andrew, Mingnan Chen, Jonathan R. McDaniel, Wenge Liu, Andrew J. Simnick, and Ashutosh Chilkoti. “Self-assembling chimeric polypeptide–doxorubicin conjugate nanoparticles that abolish tumours after a single injection.” Nature Materials 8 (2009): 993–99.
MacKay JA, Chen M, McDaniel JR, Liu W, Simnick AJ, Chilkoti A. Self-assembling chimeric polypeptide–doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nature Materials. 2009;8:993–9.
MacKay JA, Chen M, McDaniel JR, Liu W, Simnick AJ, Chilkoti A. Self-assembling chimeric polypeptide–doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nature Materials. 2009;8:993–999.

Published In

Nature Materials

Publication Date

2009

Volume

8

Start / End Page

993 / 999

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Peptides
  • Particle Size
  • Neoplasms
  • Nanotechnology
  • Nanoscience & Nanotechnology
  • Nanoparticles
  • Mice, Inbred BALB C
  • Mice
  • Drug Delivery Systems