October 2, 2006
Temperature-Sensitive Nanoparticle Boosts Drug Antitumor Activity
Using temperature-sensitive, lipid- and polymer-based nanoparticles with a polymer coating, researchers in Korea have created an anticancer drug delivery vehicle that may provide a significant boost to the therapeutic efficacy of anticancer agents, particularly when used in conjunction with hyperthermia. This work is reported in the Journal of Pharmaceutical Sciences.
Byung Shin, Ph.D., 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.
This work is detailed in a paper titled, “Hyperthermia-induced antitumor activity of thermosensitive polymer modified temperature-sensitive liposomes.” Investigators from Korea University and Chungnam National University also participated in this study. An abstract of this paper is available through PubMed.