Scdt-23. Visualization of Brain Tumor by Near-infrared Fluorescence Imaging Via Tumor-targeting Novel Peptide Identified by Phage Display
Year: 2017
Type: conference-abstract
Abstract: One of the most promising strategies to treat cancer is the specific delivery of theranostic reagents to tumor-initiating and chemoradiation-resistant cell populations for early diagnosis and eradication of tumor cells with minimizing toxicity to normal tissues. Glioblastoma stem cells (GSCs) have earned a great deal of focus due to their pivotal role in tumorigenesis and therapeutic resistance. To further develop strategies to more specifically detect and target this subpopulation of tumor cells, we employed a phage display (PhD) biopanning against GSCs to isolate tumor-homing peptides. In vitro and in vivo screening on GSCs isolated from patient GBM tumors with PhD library of 7-amino acid-length peptides recovered a consensus peptide, GBMIC2, which demonstrated strong GSC-specific affinity. To achieve efficient signal penetration through skull bone and reduce autofluorescence in biological tissues during in vivo imaging, we utilized near-infrared fluorescence with a cyanine 5.5-conjugated synthetic peptide (GBMIC2-Cy5.5) and confirmed the specificity to GSCs by flow cytometry analysis and immunocytochemistry. This peptide was also co-localized with SOX2 in GBM patient tissues. GBMIC2-Cy5.5 was delivered to subcutaneous or intracranial GBM patient-derived xenograft models via intravenous injections. Tumor specificity and dynamics of fluorescence signals were monitored and analyzed using IVIS SpectrumCT In Vivo Imaging System for 72 hours. Signals were highly specific and constant to xenografted tumors with a low intensity from normal brain and surrounding tissues. Immunohistochemistry analysis of xenografted tumors confirmed that GBMIC2-Cy5.5 was specific for tumor cells and was localized to the perivascular niche. These data corresponded to previous results matching GBMIC2 with EYA1, a protein involved in tumor cell proliferation and migration, that also localized to perivascular niche. These studies confirm the applicability of phage display biopanning to isolate tumor tropic peptides, and that GBMIC2 has the potential to selectively target GSCs for imaging and anticancer drug delivery for GBM treatment.
Source: Neuro-Oncology
Authors: Jongmyung Kim, Ping Huang, Jeremy Rich, James Liu
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2768082804