Interdisciplinary Initiatives Program Round 3 – 2006

Hongjie Dai, Chemistry
Dean Felsher, Medicine-Oncology

Carbon nanotubes have many potential biomedical applications. As inert structures with an ultra-high surface area, carbon nanotubes may be a promising delivery system for therapeutic agents. Here, we used supramolecular π-π stacking to provide very high efficiency loading of doxorubicin (DOX), a cancer chemotherapy agent, onto the sidewalls of single walled carbon nanotubes (SWNTs) functionalized by long, branched polyethylene glycol (PEG) chains. The SWNT-DOX formulation prolonged DOX circulation in the blood and markedly increased tumor specific uptake for in vivo treatment of human Burkitt lymphoma xenografts associated with a 26% increase in efficacy in the treatment of tumors over free DOX and a marked reduction in toxicity and mortality compared with free DOX. Our explanation for these findings is that SWNT-DOX was associated with decreased gastrointestinal epithelial toxicity. We conclude that supramolecular π-π stacking of a therapeutic agent onto single-walled carbon nanotubes provides a novel method to efficiently deliver high dose chemotherapy with an increase in therapeutic efficacy and a reduction in toxicity.