C 2015 American Chemical Society Use of a Lipid-CoatedMesoporous Silica Nanoparticle Platform for Synergistic

he 5 year survival rate of pancreatic ductal adenocarcinoma has remained unchanged despite significant pro-gress for other major cancers.1 One of the contributing reasons of the poor prognosis of pancreatic cancer is the resistance to chemotherapeutic agents, including gemcitabine (GEM), which is frequently used as first-line therapy.2,3 This resistance could result from acquired and/or intrinsic pathways, a dense dysplastic stroma that acts as a barrier to vascular perfusion and drug permeability, as well as unfavorable GEM pharmacokinetics as a result of insuf-ficient activation or rapid inactivation.3 Recent progress in pancreatic cancer ther-apy has been the introduction of stromal-directed agents that obliterate the dense stromal microenvironment and improve chemotherapy drug delivery. For example, an ongoing clinical trial has demonstrated that the combination of GEM with PEGy-lated hyaluronidase can overcome stromal resistance, allowing chemotherapeutic drug * Address correspondence t