Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient‐Derived Chips
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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient‐Derived Chips ; day:07 ; month:01 ; year:2022 ; extent:16
Advanced healthcare materials ; (07.01.2022) (gesamt 16)
- Creator
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Baek, Sewoom
Yu, Seung Eun
Deng, Yu‐Heng
Lee, Yong‐Jae
Lee, Dong Gue
Kim, Surim
Yoon, Seonjin
Kim, Hye‐Seon
Park, Jeongeun
Lee, Chan Hee
Lee, Jung Bok
Kong, Hyun Joon
Kang, Seok‐Gu
Shin, Young Min
Sung, Hak‐Joon
- DOI
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10.1002/adhm.202102226
- URN
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urn:nbn:de:101:1-2022010714160282913528
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:20 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Baek, Sewoom
- Yu, Seung Eun
- Deng, Yu‐Heng
- Lee, Yong‐Jae
- Lee, Dong Gue
- Kim, Surim
- Yoon, Seonjin
- Kim, Hye‐Seon
- Park, Jeongeun
- Lee, Chan Hee
- Lee, Jung Bok
- Kong, Hyun Joon
- Kang, Seok‐Gu
- Shin, Young Min
- Sung, Hak‐Joon
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