Abstract
The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received significant attention as a cancer therapeutic due to its ability to selectively trigger cancer cell apoptosis without causing toxicity in vivo. While TRAIL has demonstrated significant promise in preclinical studies in mice as a cancer therapeutic, challenges including poor circulation half-life, inefficient delivery to target sites, and TRAIL resistance have hindered clinical translation. Recent advances in drug delivery, materials science, and nanotechnology are now being exploited to develop next-generation nanoparticle platforms to overcome barriers to TRAIL therapeutic delivery. Here, we review the design and implementation of nanoparticles to enhance TRAIL-based cancer therapy. The platforms we discuss are diverse in their approaches to the delivery problem and provide valuable insight into guiding the design of future nanoparticle-based TRAIL cancer therapeutics to potentially enable future translation into the clinic.