TY - JOUR
T1 - Human Glioblastoma Visualization
T2 - Triple Receptor-Targeting Fluorescent Complex of Dye, SIWV Tetra-Peptide, and Serum Albumin Protein
AU - An, Jong Min
AU - Moon, Heejo
AU - Verwilst, Peter
AU - Shin, Jinwoo
AU - Kim, B. Moon
AU - Park, Chul Kee
AU - Kim, Jong Seung
AU - Yeo, Seung Geun
AU - Kim, Hyo Young
AU - Kim, Dokyoung
N1 - Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) of Korea funded by the Ministry of Science & ICT (NRF-2019-M3A9H1103783). This research was also supported by the Basic Science Research Program through the NRF of Korea funded by the Ministry of Education (NRF-2018-R1A6A1A03025124 and NRF-2018-R1D1A1B07043383). This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI21C0239). This research was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (MSIT) (NRF-2021M3A9I5030523). H.Y.K. acknowledges support from the Basic Science Research Program through the NRF of Korea funded by the Ministry of Education (NRF-2013-R1A6A3A01064606 and NRF-2015-R1A6A3A04059360). P.V. acknowledges support from Interne Fondsen KU Leuven/Internal Funds KU Leuven (STG/19/029). B.M.K. thanks for the financial support from the NRF of Korea (NRF-2012-M3A7B4049644). J.S.K. acknowledges support from the CRI project from the NRF of Korea funded by the Ministry of Education (NRF-2018-R1A3B1052702).
Publisher Copyright:
© 2021 American Chemical Society.
PY - 2021/6/25
Y1 - 2021/6/25
N2 - Fluorescence guided surgery (FGS) has been highlighted in the clinical site for guiding surgical procedures and providing the surgeon with a real-time visualization of the operating field. FGS is a powerful technique for precise surgery, particularly tumor resection; however, clinically approved fluorescent dyes have often shown several limitations during FGS, such as non-tumor-targeting, low in vivo stability, insufficient emission intensity, and low blood-brain barrier penetration. In this study, we disclose a fluorescent dye complex, peptide, and protein for the targeted visualization of human glioblastoma (GBM) cells and tissues. Our noble triple receptor-targeting fluorescent complex (named BSA-OXN-SIWV) consists of (i) dipolar oxazepine dye (OXN), which has high stability, low cytotoxicity, bright fluorescence, and two-photon excitable, (ii) tetra-peptide (SIWV) for the targeting of the caveolin-1 receptor, and (iii) bovine serum-albumin (BSA) protein for the targeting of albondin (gp60) and secreted protein acidic and rich in cysteine receptor. The photophysical properties and binding mode of BSA-OXN-SIWV were analyzed, and the imaging of GBM cell lines and human clinical GBM tissues were successfully demonstrated in this study. Our findings hold great promise for the application of BSA-OXN-SIWV to GBM identification and the surgery at clinical sites, as a new FGS agent.
AB - Fluorescence guided surgery (FGS) has been highlighted in the clinical site for guiding surgical procedures and providing the surgeon with a real-time visualization of the operating field. FGS is a powerful technique for precise surgery, particularly tumor resection; however, clinically approved fluorescent dyes have often shown several limitations during FGS, such as non-tumor-targeting, low in vivo stability, insufficient emission intensity, and low blood-brain barrier penetration. In this study, we disclose a fluorescent dye complex, peptide, and protein for the targeted visualization of human glioblastoma (GBM) cells and tissues. Our noble triple receptor-targeting fluorescent complex (named BSA-OXN-SIWV) consists of (i) dipolar oxazepine dye (OXN), which has high stability, low cytotoxicity, bright fluorescence, and two-photon excitable, (ii) tetra-peptide (SIWV) for the targeting of the caveolin-1 receptor, and (iii) bovine serum-albumin (BSA) protein for the targeting of albondin (gp60) and secreted protein acidic and rich in cysteine receptor. The photophysical properties and binding mode of BSA-OXN-SIWV were analyzed, and the imaging of GBM cell lines and human clinical GBM tissues were successfully demonstrated in this study. Our findings hold great promise for the application of BSA-OXN-SIWV to GBM identification and the surgery at clinical sites, as a new FGS agent.
KW - albumin complex
KW - fluorescence-guided surgery
KW - fluorescent probe
KW - glioblastoma targeting
KW - two-photon microscopy
UR - http://www.scopus.com/inward/record.url?scp=85109038104&partnerID=8YFLogxK
U2 - 10.1021/acssensors.1c00320
DO - 10.1021/acssensors.1c00320
M3 - Article
C2 - 34100604
AN - SCOPUS:85109038104
VL - 6
SP - 2270
EP - 2280
JO - ACS Sensors
JF - ACS Sensors
SN - 2379-3694
IS - 6
ER -