Nanoparticles Enhance Combination Chemotherapy
and Radiation Therapy
A mixture of current drugs and carbon nanoparticles shows potential to enhance treatment for head and neck cancers, especially when combined with radiation therapy, according to new research conducted by investigators at Rice University and the University of Texas MD Anderson Cancer Center. The therapy uses carbon nanoparticles to encapsulate chemotherapeutic drugs and sequester them until they are delivered to the cancer cells they are meant to kill.
The new strategy, developed by a team led by James Tour and Jeffrey Myers of Rice, is detailed in a paper published in the journal ACS Nano. This therapy combines paclitaxel and Cetuximab with hydrophilic carbon nanoparticles functionalized with a form of the biocompatible polymer polyethylene glycol that is known as PEG-HCC.
Cetuximab, the targeting agent, is a humanized monoclonal antibody that binds exclusively to the epidermal growth factor receptor (EGFR), a cell-surface receptor overexpressed by 90% of head and neck squamous cell cancers. Paclitaxel, an active agent in chemotherapy, is used to treat lung, ovarian, breast, and head and neck cancers.
Because paclitaxel is hydrophobic – it won't mix with water – the substances are generally combined with Cremophor EL, a castor oil-based carrier that allows the compound marketed as Taxol to be delivered intravenously to patients. Toxicities associated with Chremophor can limit paclitaxel's effectiveness, however.
Tour, Myers and their associates have found a simple way to mix paclitaxel and Cetuximab with carbon nanoparticles that adsorb the active ingredients. The new construct, which readily self-assembles, is water-soluble and is more effective at targeting tumors than Taxol alone while avoiding the toxic effects of paclitaxel and Cremophor on adjacent healthy cells.
Tests in mice showed that when this new construct was administered along with radiation, the combination resulted in a significant boost in tumor destruction. The researchers hypothesize that that paclitaxel, the chemotherapy drug, sensitizes the cancer cells to the effects of radiation and the Cetuximab/PEG-HCC increases the delivery of paclitaxel to cancer cells.
Unlike Cremophor, the enhanced carbon nanoparticles appear to be nontoxic. Biodistribution and toxicity studies showed the "large majority" of PEG-HCC nanoparticles are excreted through the kidneys, while trace amounts in the livers and spleens of mice tested showed no damage to the organs.
This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, "Noncovalent assembly of targeted carbon nanovectors enables synergistic drug and radiation cancer therapy in vivo." An abstract of this paper is available at the journal's website.