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This study outlines a drug delivery mechanism that utilizes two independent vehicles, allowing for delivery of chemically and physically distinct agents. The mechanism was utilized to deliver a new anti-cancer combination therapy consisting of piperlongumine (PL) and TRAIL to treat PC3 prostate cancer and HCT116 colon cancer cells. PL, a small-molecule hydrophobic drug, was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles. TRAIL was chemically conjugated to the surface of liposomes. PL was first administered to sensitize cancer cells to the effects of TRAIL. PC3 and HCT116 cells had lower survival rates in vitro after receiving the dual nanoparticle therapy compared to each agent individually. In vivo testing involved a subcutaneous mouse xenograft model using NOD-SCID gamma mice and HCT116 cells. Two treatment cycles were administered over 48 hours. Higher apoptotic rates were observed for HCT116 tumor cells that received the dual nanoparticle therapy compared to individual stages of the nanoparticle therapy alone.

This article discusses the role of the protein corona in delivery systems with tagged nanoparticles and how knowledge of the protein corona can help in optimizing delivery. The basic question is whether and how the binding of proteins and other biomolecules at the nanoparticle surface interfere with the interaction between a tag and its receptor. This is an interesting problem in many respects, but most intriguing are the observed differences in delivery efficiency in vivo compared with protein-free in vitro conditions. In order to understand possible situations that the nanoparticle will face in a protein-rich biological environment, we will first describe the formation of a protein corona and thereafter discuss potential perturbations of the delivery systems when moving from in vitro testing to in vivo applications. We emphasize the role of mathematical modeling in optimizing the design of functionalized nanoparticles to achieve high success of delivery.