Open AccessCoupling tumor necrosis factor‐related apoptosis‐inducing ligand to iron oxide nanoparticles increases its apoptotic activity on HCT116 and HepG2 malignant cells: effect of magnetic core size
Author(s) -
Belkahla Hanene,
Haque Amranul,
Revzin Alexander,
Gharbi Tijani,
Constantinescu Andrei Alexandru,
Micheau Olivier,
Hémadi Miryana,
Ammar Souad
Publication year - 2019
Publication title -
journal of interdisciplinary nanomedicine
Language(s) - English
Resource type - Journals
ISSN - 2058-3273
DOI - 10.1002/jin2.55
Subject(s) - apoptosis , cytotoxicity , chemistry , tumor necrosis factor alpha , annexin , cancer research , ligand (biochemistry) , necrosis , programmed cell death , cancer cell , biophysics , receptor , cancer , biochemistry , immunology , biology , medicine , in vitro
Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) has been considered as a potential anticancer agent owing to its selectivity for malignant cells. However, its clinical use remains limited because of its poor efficacy. Attempts to increase its antitumor activity include, among others, its functionalization by nanoparticles (NPs). In the present study, TRAIL was grafted onto magnetic spinel iron oxide NPs of defined core size, 10 and 100 nm on average, to see whether the size of the resulting nanovectors, NV10 and NV100, respectively, might affect TRAIL efficacy and selectivity. Apoptosis induced by NV10 and NV100 was higher than by TRAIL alone in both HCT116 and HepG2 cells. At equimolar concentrations, neither the nanovectors nor the corresponding NPs displayed cytotoxicity towards normal primary hepatocytes or TRAIL receptor‐deficient HCT116 cells. NV100 exhibited superior proapoptotic activity than NV10, as evidenced by methylene blue and annexin V staining. Consistently, both caspase activation and TRAIL death‐induced signaling complex formation, as assessed by immunoblot analysis, were found to be increased in cells treated with NV100 as compared with NV10 or TRAIL alone. These results suggest that the size of NPs is important when TRAIL is vectorized for cancer therapy.