Byung Shin, Ph.D., from the Korea Research Institute of Chemical Technology led the research team that developed a temperature-sensitive nanoparticle for delivering doxorubicin to tumors. This particular liposome falls apart and releases its therapeutic payload at temperatures that are slightly elevated from normal body temperature. A polymer coating, made from either poly(ethylene glycol) or poly(N-isopropylacrylamide-co-acrylamide), enhanced the stability of the liposomes in serum by inhibiting the amount of protein that sticks to the nanoparticle. The nanoparticles that the researchers developed contain between 50 - 60% doxorubicin by weight.
The investigators first studied the release properties of these nanoparticles, demonstrating that they release very little drug at 37°C, normal body temperature. However, at 38°C, drug release soared rapidly as a result of a dramatic change in the stability of the nanoparticles.
Next, the researchers evaluated tumor response to the doxorubicin-loaded, temperature-sensitive nanoparticles. To assess antitumor activity, the investigators treated mice with human melanoma tumors with saline, plain doxorubicin, or the doxorubicin-nanoparticle formulation, and then measured how much the tumors grew over nine days after a single intravenous injection. The researchers also tracked the effects of a single hyperthermia treatment given one hour after drug injection. The results of this study showed clearly that the drug-nanoparticle formulation in combination with hyperthermia was far superior to any of the other treatments tested.