Two-stage nanoparticle delivery of piperlongumine, TRAIL anti-cancer therapy

"We have found that liposomal TRAIL shows great promise for the destruction of tumor cells in the bloodstream, lymphatic system, and also in solid tumors," says Daljit S. and Elaine Sarkaria Professor Michael R. King, Ph.D., of Cornell University and senior author of the study.

In the paper, the Cornell researchers describe a nanoparticle-based drug delivery mechanism developed for a combination cancer therapy. Nanoparticle delivery platforms have been previously pursued for a variety of cancer therapies. A number of studies have focused on complex particle structures and designs aimed at improving delivery. The Cornell group's system utilizes a different approach through the use of a dual nanoparticle delivery mechanism. Therapeutic components were administered through separate particles as opposed to delivering the agents in a single particle. Given the hydrophobic nature of the TRAIL sensitizer, the drug was encapsulated in polymer-based nanoparticles.

In the study, researchers observed of a higher number of apoptotic cells in mouse trials, consistent with their observed laboratory results that demonstrated an increased therapeutic efficacy when utilizing the two-stage nanoparticle therapy compared to each individual nanoparticle stage alone. The dual nanoparticle delivery system provided a level of flexibility when administering the two stages of the therapy, allowing for an opportunity for sensitization of the tumor cells prior to administering the second component of the therapy.

The team from Cornell is working now to develop a new therapeutic approach to target cancer cells in the bloodstream for the prevention of prostate cancer metastasis, that utilizes circulating leukocytes as a carrier for the apoptosis ligand TRAIL. Once introduced into the bloodstream, E-selectin/TRAIL liposomes attach to the surface of peripheral blood leukocytes, to render these "unnatural killer cells" cytotoxic to circulating cancer cells without affecting blood cell or endothelial cell viability. They previously showed that viable cancer cells can be rapidly cleared from the bloodstream, using liposome-bound TRAIL concentrations that are two orders of magnitude lower than the dosages used in prior human clinical trials of soluble TRAIL protein. More recently, they have found that E-selectin/TRAIL liposomes can completely block metastasis and also shrink primary prostate cancer tumors in mice.