PurposeWe developed a new nanoparticle formulation comprised of human serum albumin (HSA) for co-delivery of doxorubicin (Dox) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the goal of apoptotic synergy in the treatment of colon cancer.MethodsTRAIL (0.2, 0.4, 1.0%)- and Dox-loaded HSA nanoparticles (TRAIL/Dox HSA NPs) were prepared by using the nabTM technology. Morphological and physicochemical characterizations were investigated by dynamic light scattering and transmission electron microscopy. Synergistic cytotoxicity, apoptotic activity, and potential penetration into mass tumor were determined in HCT116 cell-based systems. Furthermore, antitumor efficacy and tumor targeting were also investigated.ResultsTRAIL/Dox HSA NPs were uniformly spherical with sizes of 60?~?120 nm. The encapsulation efficacy of Dox and TRAIL was 68.9–77.2% and 80.4–86.0%, respectively. TRAIL 1.0%/Dox HSA NPs displayed the best inhibition of HCT116 colon cancer cells; inhibition was 6 times higher than achieved with Dox HSA NPs. The TRAIL 1.0%/Dox HSA NPs formulation was studied further. Flow cytometry analysis and TUNEL assay revealed that TRAIL 1.0%/Dox HSA NPs had markedly greater apoptotic activity than Dox HSA NPs. In HCT116 tumor-bearing BALB/c nu/nu mice, TRAIL 1.0%/Dox HSA NPs had significantly higher antitumor efficacy than Dox HSA NPs (tumor volume; 933.4 mm3 vs. 3183.7 mm3, respectively). TRAIL 1.0%/Dox HSA NPs penetrated deeply into tumor masses in a HCT116 spheroid model and localized in tumor sites after tail vein injection.ConclusionsData indicate that TRAIL 1.0%/Dox HSA NPs offer advantages of co-delivery of Dox and TRAIL in tumors, with potential synergistic apoptosis-based anticancer therapy. |