Improved Stability, Antitumor Effect, and Controlled Release of Recombinant Soluble TRAIL by Combining Genetic...

Soluble tumor necrosis factor related apoptosis-inducing ligand (sTRAIL) is a promising candidate for antitumor protein drugs. However, the low stability and poor pharmacokinetic profile significantly limit its clinical application. In this work, a novel strategy was used to improve sTRAIL performance by combining genetic engineering with coaxial electrospinning. We first obtained a stable homotrimer via genetic engineering using the adenovirus knobless fiber motif to modify sTRAIL. In vitro studies showed that the engineered sTRAIL was more stable and had higher antitumor activity than wild sTRAIL. This new recombinant sTRAIL was then encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanofibers by coaxial electrospinning to further enhance the stability and achieve the controlled release of sTRAIL. Surprisingly, the recombinant sTRAIL maintained its biological activity during the electrospinning process and exhibited a good cumulative release. The establishment of incorporation treatment of breast cancer mouse model demonstrated that the PLGA/sTRAIL nanofiber mats can effectively inhibit the growth of breast cancer tumor cells.