Supramolecular nanoparticles generated by the self-assembly of polyrotaxanes for antitumor drug delivery

Int J Nanomedicine. 2012:7:5249-58. doi: 10.2147/IJN.S33649. Epub 2012 Oct 5.

Abstract

A new approach of fabricating supramolecular nanoparticles generated by self-assembly polyrotaxanes for antitumor drug delivery has been reported. Cinnamic-acid-modified poly(ethylene glycol) chains were threaded in α-cyclodextrins to form polyrotaxanes. The polyrotaxanes self-assembled supramolecular nanoparticles. The morphology of the nanoparticles was changed from nanovesicle to micelle after the antitumor drug, doxorubicin, was loaded. The release profile of the drug-loaded nanoparticles was investigated, and it was found that the sustaining release time could last for 32 hours. The drug-loaded nanoparticles were co-cultured with mouse 4T1 breast cancer cells with a drug concentration of 10 μg/mL; the cell survival rate was 3.3% after a 72-hour incubation. In an in vivo study of breast cancer in a mouse model, the drug-loaded nanoparticles were injected in the tail veins of mice with a dose of 5 mg/kg body weight. The tumor inhibition rate of drug-loaded nanoparticles was 53%, which was better than that of doxorubicin hydrochloride. The cardiac toxicity of doxorubicin was decreased greatly after the encapsulation into supramolecular polyrotaxane nanoparticles.

Keywords: doxorubicin; nanoparticle; polyrotaxane; self-assembly; supermolecular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Crystallization / methods*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Macromolecular Substances / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Nanocapsules / administration & dosage*
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Rotaxanes / chemistry*

Substances

  • Antineoplastic Agents
  • Macromolecular Substances
  • Nanocapsules
  • Rotaxanes
  • Doxorubicin