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Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient-Derived Chips

Authors
 Sewoom Baek  ;  Seung Eun Yu  ;  Yu-Heng Deng  ;  Yong-Jae Lee  ;  Dong Gue Lee  ;  Surim Kim  ;  Seonjin Yoon  ;  Hye-Seon Kim  ;  Jeongeun Park  ;  Chan Hee Lee  ;  Jung Bok Lee  ;  Hyun Joon Kong  ;  Seok-Gu Kang  ;  Young Min Shin  ;  Hak-Joon Sung 
Citation
 ADVANCED HEALTHCARE MATERIALS, Vol.11(8) : e2102226, 2022-04 
Journal Title
ADVANCED HEALTHCARE MATERIALS
ISSN
 2192-2640 
Issue Date
2022-04
MeSH
Animals ; Brain Neoplasms* / pathology ; Cell Line, Tumor ; Drug Resistance ; Epigenesis, Genetic ; Glioblastoma* / drug therapy ; Glioblastoma* / metabolism ; Humans ; Hypoxia ; Mice
Keywords
3D glioblastoma chip ; drug resistance ; epigenetic alterations ; hypoxia rescue ; oxygen-releasing microparticles
Abstract
Glioblastoma (GBM) is one of the most intractable tumor types due to the progressive drug resistance upon tumor mass expansion. Incremental hypoxia inside the growing tumor mass drives epigenetic drug resistance by activating nongenetic repair of antiapoptotic DNA, which could be impaired by drug treatment. Hence, rescuing intertumor hypoxia by oxygen-generating microparticles may promote susceptibility to antitumor drugs. Moreover, a tumor-on-a-chip model enables user-specified alternation of clinic-derived samples. This study utilizes patient-derived glioblastoma tissue to generate cell spheroids with size variations in a 3D microchannel network chip (GBM chip). As the spheroid size increases, epigenetic drug resistance is promoted with inward hypoxia severance, as supported by the spheroid size-proportional expression of hypoxia-inducible factor-1a in the chip. Loading antihypoxia microparticles onto the spheroid surface significantly reduces drug resistance by silencing the expression of critical epigenetic factor, resulting in significantly decreased cell invasiveness. The results are confirmed in vitro using cell line and patient samples in the chip as well as chip implantation into a hypoxic hindlimb ischemia model in mice, which is an unprecedented approach in the field.
Full Text
https://onlinelibrary.wiley.com/doi/10.1002/adhm.202102226
DOI
10.1002/adhm.202102226
Appears in Collections:
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
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Sung, Hak-Joon(성학준) ORCID logo https://orcid.org/0000-0003-2312-2484
Shin, Young Min(신영민)
Yu, Seung Eun(유승은)
Yoon, Seon Jin(윤선진) ORCID logo https://orcid.org/0000-0002-3255-5081
Lee, Yong Jae(이용재) ORCID logo https://orcid.org/0000-0003-0297-3116
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189318
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