Tissue Niche Miniature of Glioblastoma Patient Treated with Nano-Awakeners to Induce Suicide of Cancer Stem Cells

• Published in: Advanced healthcare materials Vol. 11; no. 21; p. e2201586
• Main Authors: Yoon, Seon-Jin, Baek, Sewoom, Yu, Seung Eun, Jo, Euna, Lee, Dongkyu, Shim, Jin-Kyoung, Choi, Ran Joo, Park, Junseong, Moon, Ju Hyung, Kim, Eui-Hyun, Chang, Jong Hee, Lee, Jung Bok, Park, Joon-Sang, Sung, Hak-Joon, Kang, Seok-Gu
• Format: Journal Article
• Language: English
• Published: Germany 01.11.2022
• Subjects: Brain Neoplasms - metabolism; Cell Line, Tumor; Glioblastoma - metabolism; Humans; Neoplastic Stem Cells; Suicide; Temozolomide - pharmacology; Tumor Microenvironment; RNA sequencing; drug response; glioblastoma patient-tissue chip culture; PTPRZ1; nanotherapy
• ISSN: 2192-2659
• DOI: 10.1002/adhm.202201586

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.