Development of therapeutic strategies to overcome fibrotic barriers to nanomedicine delivery in pancreatic cancer
Summary
The neovasculature of tumors are immature and lymphatics underdeveloped. This gives rise to the enhanced permeability & retention (EPR) effect, in which nanomedicines (drugs formulated in sizes ranging from ten to a few hundred nanometers) specifically accumulate in tumors while sparing normal tissues. The EPR effect is the theoretical foundation for the development of nanomedicines against tumors, and it is expected nanomedicines will be an ideal chemotherapeutic strategy--one that is both effective and safe. However, in pancreatic cancer, which is notorious for its dismal prognosis, prominent fibrosis within the tumor tissue acts as a barrier to nanomedicine delivery and limits its efficacy. The first aim of this study is to elucidate the mechanisms by which extracellular matrix signaling contributes to the generation of fibrotic barriers to nanomedicine delivery in pancreatic cancer. Second, novel strategies targeting the fibrotic barrier will be developed to enhance nanomedicine delivery.
