Abstract
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.
Highlights
Glioblastoma (GBM) is the most common and aggressive form of brain tumor, which is characterized by the least favorable prognosis—the average survival rate for patients with this diagnosis is 15 months [1]
Standard methods such as surgery, radiation therapy and chemotherapy are used to treat glioblastoma, and in most cases these methods are ineffective. Such a low efficiency of glioblastoma treatment is often associated with two characteristic features of this tumor: the invasion of tumor cells into the brain parenchyma, which leads to the emergence of secondary tumor foci, and the high heterogeneity of tumor
Targeted therapy based on the use of drugs affecting specific types of tumors can be a solution to the problem of the low efficiency of the applied cancer therapies, which makes it possible to increase the effectiveness of treatment and minimize toxic effects on healthy tissues
Summary
Glioblastoma (GBM) is the most common and aggressive form of brain tumor, which is characterized by the least favorable prognosis—the average survival rate for patients with this diagnosis is 15 months [1]. Standard methods such as surgery, radiation therapy and chemotherapy are used to treat glioblastoma, and in most cases these methods are ineffective. Such a low efficiency of glioblastoma treatment is often associated with two characteristic features of this tumor: the invasion of tumor cells into the brain parenchyma, which leads to the emergence of secondary tumor foci, and the high heterogeneity of tumor. The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor and ensure the implementation of the targeted approach. Short peptides are considered promising agents for the delivery of therapeutic and diagnostic molecules to cancer cells, which have high affinity and specificity for the target and a higher efficiency of penetration into cancer cells as compared to ligands of larger sizes, for example, antibodies
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