Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery.

Journal: 
Proc Natl Acad Sci U S A
Publication Year: 
2016
Authors: 
Xinyi Jiang
Sergio Fitch
Christine Wang
Christy Wilson
Jianfeng Li
Gerald A Grant
Fan Yang
PubMed link: 
27849590
Public Summary: 
Current treatment for glioblastoma multiforme (GBM) fails to address its highly infiltrative nature; treatment often leaves behind microscopic neoplastic satellites, resulting in eventual tumor recurrence. Here we report polymeric nanoparticle-engineered human adipose-derived stem cells (hADSCs) overexpressing the cancer-specific TNF-related apoptosis-inducing ligand for targeting and eradicating glioblastoma cells. Engineered hADSCs exhibited long-range directional migration toward tumor in patient-derived GBM orthotropic xenografts and showed significant inhibition of tumor growth and extension of animal survival. Repetitive injection further prolonged animal survival compared with single injection. Together, our data suggest that nanoparticle-engineered hADSCs exhibit the therapeutically relevant behavior of “seek-and-destroy” tumortropic migration, and may offer a promising therapy for substantial enhancement of GBM treatment.
Scientific Abstract: 
Glioblastoma multiforme (GBM) is one of the most intractable of human cancers, principally because of the highly infiltrative nature of these neoplasms. Tracking and eradicating infiltrating GBM cells and tumor microsatellites is of utmost importance for the treatment of this devastating disease, yet effective strategies remain elusive. Here we report polymeric nanoparticle-engineered human adipose-derived stem cells (hADSCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as drug-delivery vehicles for targeting and eradicating GBM cells in vivo. Our results showed that polymeric nanoparticle-mediated transfection led to robust up-regulation of TRAIL in hADSCs, and that TRAIL-expressing hADSCs induced tumor-specific apoptosis. When transplanted in a mouse intracranial xenograft model of patient-derived glioblastoma cells, hADSCs exhibited long-range directional migration and infiltration toward GBM tumor. Importantly, TRAIL-overexpressing hADSCs inhibited GBM growth, extended survival, and reduced the occurrence of microsatellites. Repetitive injection of TRAIL-overexpressing hADSCs significantly prolonged animal survival compared with single injection of these cells. Taken together, our data suggest that nanoparticle-engineered TRAIL-expressing hADSCs exhibit the therapeutically relevant behavior of "seek-and-destroy" tumortropic migration and could be a promising therapeutic approach to improve the treatment outcomes of patients with malignant brain tumors.