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

 Seon-Jin Yoon  ;  Sewoom Baek  ;  Seung Eun Yu  ;  Euna Jo  ;  Dongkyu Lee  ;  Jin-Kyoung Shim  ;  Ran Joo Choi  ;  Junseong Park  ;  Ju Hyung Moon  ;  Eui-Hyun Kim  ;  Jong Hee Chang  ;  Jung Bok Lee  ;  Joon-Sang Park  ;  Hak-Joon Sung  ;  Seok-Gu Kang 
 ADVANCED HEALTHCARE MATERIALS, Vol.11(21) : e2201586, 2022-11 
Journal Title
Issue Date
Brain Neoplasms* / metabolism ; Cell Line, Tumor ; Glioblastoma* / metabolism ; Humans ; Neoplastic Stem Cells ; Suicide* ; Temozolomide / pharmacology ; Tumor Microenvironment
PTPRZ1 ; RNA sequencing ; drug response ; glioblastoma patient-tissue chip culture ; nanotherapy
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.
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1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Kim, Eui Hyun(김의현) ORCID logo https://orcid.org/0000-0002-2523-7122
Moon, Ju Hyung(문주형)
Park, Junseong(박준성)
Sung, Hak-Joon(성학준) ORCID logo https://orcid.org/0000-0003-2312-2484
Yu, Seung Eun(유승은) ORCID logo https://orcid.org/0000-0002-9690-8739
Yoon, Seon Jin(윤선진) ORCID logo https://orcid.org/0000-0002-3255-5081
Chang, Jong Hee(장종희) ORCID logo https://orcid.org/0000-0003-1509-9800
Choi, Ran Joo(최란주)
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