Rational design of "heat seeking" drug loaded polypeptide nanoparticles that thermally target solid tumors

Nano Lett. 2014 May 14;14(5):2890-5. doi: 10.1021/nl5009376. Epub 2014 Apr 21.

Abstract

This paper demonstrates the first example of targeting a solid tumor that is externally heated to 42 °C by "heat seeking" drug-loaded polypeptide nanoparticles. These nanoparticles consist of a thermally responsive elastin-like polypeptide (ELP) conjugated to multiple copies of a hydrophobic cancer drug. To rationally design drug-loaded nanoparticles that exhibit thermal responsiveness in the narrow temperature range between 37 and 42 °C, an analytical model was developed that relates ELP composition and chain length to the nanoparticle phase transition temperature. Suitable candidates were designed based on the predictions of the model and tested in vivo by intravital confocal fluorescence microscopy of solid tumors, which revealed that the nanoparticles aggregate in the vasculature of tumors heated to 42 °C and that the aggregation is reversible as the temperature reverts to 37 °C. Biodistribution studies showed that the most effective strategy to target the nanoparticles to tumors is to thermally cycle the tumors between 37 and 42 °C. These nanoparticles set the stage for the targeted delivery of a range of cancer chemotherapeutics by externally applied mild hyperthermia of solid tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Drug Delivery Systems
  • Elastin / administration & dosage
  • Elastin / chemistry*
  • Humans
  • Hyperthermia, Induced
  • Mice
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Peptides / administration & dosage
  • Peptides / chemistry
  • Temperature

Substances

  • Antineoplastic Agents
  • Peptides
  • Elastin