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

Nat Mater. 2009 Dec;8(12):993-9. doi: 10.1038/nmat2569. Epub 2009 Nov 8.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / therapeutic use
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Doxorubicin / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Delivery Systems / methods
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Nanotechnology
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Particle Size
  • Peptides / administration & dosage
  • Peptides / chemistry*
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Peptides
  • Doxorubicin