Tissue Niche Miniature of Glioblastoma Patient Treated with Nano-Awakeners to Induce Suicide of Cancer Stem Cells.
Seon-Jin YoonSewoom BaekSeung Eun YuEuna JoDongkyu LeeJin-Kyoung ShimRan Joo ChoiJunseong ParkJu Hyung MoonEui-Hyun KimJong Hee ChangJung Bok LeeJoon-Sang ParkHak-Joon SungSeok-Gu KangPublished in: Advanced healthcare materials (2022)
Patient-specific cancer therapies can evolve by vitalizing the mother tissue-like cancer niche, cellular profile, genetic signature, and drug responsiveness. This evolution has enabled the elucidation of a key mechanism along with development of the mechanism-driven therapy. After surgical treatment, glioblastoma (GBM) patients require prompt therapy within 14 days in a patient-specific manner. Hence, this study approaches direct culture of GBM patient tissue (1 mm diameter) in a microchannel network chip. Cancer vasculature-mimetic perfusion can support the preservation of the mother tissue-like characteristic signatures and microenvironment. When temozolomide and radiation are administered within 1 day, the responsiveness of the tissue in the chip reflected the clinical outcomes, thereby overcoming the time-consuming process of cell and organoid culture. When the tissue chip culture is continued, the intact GBM signature gets lost, and the outward migration of stem cells from the tissue origin increases, indicating a leaving-home effect on the family dismantle. Nanovesicle production using GBM stem cells enables self-chasing of the cells that escape the temozolomide effect owing to quiescence. The anti-PTPRZ1 peptide display and temozolomide loading to nanovesicles awakes cancer stem cells from the quiescent stage to death. This study suggests a GBM clinic-driven avatar platform and mechanism-learned nanotherapy for translation.
Keyphrases
- papillary thyroid
- stem cells
- newly diagnosed
- high throughput
- squamous cell
- magnetic resonance imaging
- chronic kidney disease
- primary care
- cancer stem cells
- cell death
- emergency department
- single cell
- radiation therapy
- oxidative stress
- gene expression
- copy number
- young adults
- case report
- peritoneal dialysis
- adverse drug
- contrast enhanced
- cell cycle arrest
- drug induced
- neural stem cells