Pancreatic cancer is among the most lethal forms of cancer, in large part due to a mucus-like membrane, called stroma, which develops on the tumor surface. The most effective chemotherapeutic agent, gemcitabine, shows only a 20% efficacy in penetrating the tumor.  This, coupled with the harsh side effects, which are carried by the drug, results in a survival rate of less than 5%.  Here, we present a method for delivering the drug that offers mitigation of the side effects as well as a targeted delivery and controlled release of the drug, improving its overall efficacy. The modification of gold nanoparticle (AuNP) surface with self-assembled functional thiols has enabled us to immobilize gemcitabine on the nanoparticle nanocarriers through a strong amide bond formation. This bond prevents the drug from being metabolized and from acting on tissue at physiological pH of 7.4. However, the bond becomes unstable at lower pH, encountered in cancer cells, and will break, releasing the drug in a cancer tissue. Further functionalization of the nanoparticles with folic acid and transferrin offers a targeted delivery, since the cancer cells overexpress folate and transferrin receptors that can anchor the drug nanocarriers on a cancer cell membrane and mediate their endocytosis.  Thus, through the modification of gold nanoparticles, we were able to synthesize a nanocarrier containing gemcitabine and folic acid/transferrin that is capable of targeted controlled-release delivery of the drug, reducing the side effects of the drug and increasing its efficacy.

Folic acid- and transferrin-functionalized gold nanoparticles for targeted delivery and controlled release of anti-cancer drug Gemcitabine

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.