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.
|Journal||Advanced Healthcare Materials|
|Publication status||Published - 2022 Nov 2|
Bibliographical noteFunding Information:
S.‐J.Y., S.B., and S.E.Y. contributed equally to this work. This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety (Project Number:1711138302, KMDF_PR_20200901_0152‐01), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF‐2019R1A2C2010802) to H.J.S. National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (NRF‐2022R1A2B5B03001199), the Ministry of Science and ICT (NRF‐2020M2D9A2092372), the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF‐2020M3E5E2037960), and the “Team Science Award” of Yonsei University College of Medicine (6‐2021‐0192) to S.G.K. Figure illustrations were created with BioRender.com.
© 2022 Wiley-VCH GmbH.
All Science Journal Classification (ASJC) codes
- Biomedical Engineering
- Pharmaceutical Science