Phage-derived protein-mediated targeted chemotherapy of pancreatic cancer

Abstract

Pancreatic cancer has been a life-threatening illness associated with high incidence and mortality rates. Paclitaxel (PCT) that causes mitotic arrest in cancer cells disrupting microtubule function is used for pancreatic cancer treatment. Nausea, anorexia and abdominal pain are some of the typical dose-limiting toxicity associated gastrointestinal side effects of the drug. Here, we present the use of polymeric mixed micelles to enable a targeted delivery of PCT and to provide additional advantages such as enhanced drug solubility, bioavailability and minimal dose-limiting toxicity. Also, these micelles self-assemble with pancreatic cancer cells-specific phage proteins P38, L1 and with the hydrophobic drug PCT resolving the issue of complex chemistry efforts normally needed for any conjugation. Our cytotoxicity and binding experiment results in vitro in 2 D and 3 D models suggested that the phage protein-targeted drug-loaded micelles bind and exhibit higher cell killing over the non-targeted ones.

Keywords:

• Cancer targeting
• nanoparticles
• paclitaxel
• pharmacokinetics
• targeted drug delivery
• polymeric micelles
• pancreatic cancer
• self-assembling
• in vitro uptake and cytotoxicity studies
• spheroid model

Additional information

Funding

This work was supported by NIH grant # R01 CA125063-01 and the Animal Health and Disease Research grant 2006-9, College of Veterinary Medicine, Auburn University to Valery A. Petrenko and by NIH grant #1U54CA151881 to Vladimir P. Torchilin.