Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ijms22010314
Keywords
phage display; glioblastoma; tumor-targeting peptides; cancer stem cells (CSCs); CD133; CD44; immunocytochemistry; fluorescence-activated cell sorting (FACS)
Funding
- Russian Science Fund [19-44-02006]
- Russian Science Foundation [19-44-02006] Funding Source: Russian Science Foundation
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The study utilized phage display to search for tumor-specific ligands, with in vivo screening of linear phage peptide libraries proving to be the most effective strategy for obtaining tumor-targeting peptides capable of targeted delivery to glioblastoma.
Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.
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