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

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:

• polyrotaxane
• self-assembly
• nanoparticle
• doxorubicin
• supermolecular

Acknowledgments

This research work was supported by the National Basic Research Program of China (National 973 program, No 2011CB606206), the National Science Foundation of China (NSFC, No 31070849, 50830105, 51133004), the Program for New Century Excellent Talents in University, Ministry of Education (MOE, NCET-10-0564), the International Collaboration Project of Ministry of Science and Technology (MOST, No 2010DFA51550), the Program for Changjiang Scholars, and the Innovative Research Team in University (IRT1163).

Disclosure

The authors report no conflicts of interest in this work.