Extra-domain B of fibronectin as an alternative target for drug delivery and a cancer diagnostic and prognostic biomarker for malignant glioma
- Authors
- Saw, Phei Er; Xu, Xiaoding; Kang, Bo Ram; Lee, Jungsul; Lee, Yeo Song; Kim, Chungyeul; Kim, Hyungsin; Kang, Shin-Hyuk; Na, Yoo Jin; Moon, Hong Joo; Kim, Joo Han; Park, Youn-Kwan; Yoon, Wonki; Kim, Jong Hyun; Kwon, Taek-Hyun; Choi, Chulhee; Jon, Sangyong; Chong, Kyuha
- Issue Date
- 11월-2021
- Publisher
- IVYSPRING INT PUBL
- Keywords
- EDB-Fibronectin; Glioma; Big Data; Biomarkers; Micelles
- Citation
- THERANOSTICS, v.11, no.2, pp.941 - 957
- Indexed
- SCIE
SCOPUS
- Journal Title
- THERANOSTICS
- Volume
- 11
- Number
- 2
- Start Page
- 941
- End Page
- 957
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/50656
- DOI
- 10.7150/thno.44948
- ISSN
- 1838-7640
- Abstract
- Extra-domain B of fibronectin (EDB-FN) is an alternatively spliced form of fibronectin with high expression in the extracellular matrix of neovascularized tissues and malignant cancer cells. In this study, we evaluated the practicality of using EDB-FN as a biomarker and therapeutic target for malignant gliomas (MGs), representative intractable diseases involving brain tumors. Methods: The microarray- and sequence-based patient transcriptomic database 'Oncopression' and tissue microarray of MG patient tissue samples were analyzed. EDB-FN data were extracted and evaluated from 23,344 patient samples of 17 types of cancer to assess its effectiveness and selectivity as a molecular target. To strengthen the results of the patient data analysis, the utility of EDB-FN as a molecular marker and target for MG was verified using active EDB-FN-targeting ultrasmall lipidic micellar nanoparticles (similar to 12 nm), which had a high drug-loading capacity and were efficiently internalized by MG cells in vitro and in vivo. Results: Brain tumors had a 1.42-fold cancer-to-normal ratio (p < 0.0001), the second highest among 17 cancers after head and neck cancer. Patient tissue microarray analysis showed that the EDB-FN high-expression group had a 5.5-fold higher risk of progression than the EDB-FN low-expression group (p < 0.03). By labeling docetaxel-containing ultrasmall micelles with a bipodal aptide targeting EDB-FN (termed APT(EDB)-DSPE-DTX), we generated micelles that could specifically bind to MG cells, leading to superior antitumor efficacy of EDB-FN-targeting nanoparticles compared to nontargeting controls. Conclusions: Taken together, these results show that EDB-FN can be an effective drug delivery target and biomarker for MG.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
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