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2016 ; 29
(3
): 93-103
Nephropedia Template TP
Protein Eng Des Sel
2016[Mar]; 29
(3
): 93-103
PMID26764410
show ga
Cancer cell-specific targeting ligands against numerous cancer cell lines have
been selected previously and used as ligands for cell-specific delivery of
chemotherapies and various nanomedicines. However, tumor heterogeneity is one
recognized problem hampering clinical translation of targeted anti-cancer
medicines. Therefore, a novel class of targeting ligands is required that
recognize receptors expressed between a variety of cancer phenotypes, identified
here as 'promiscuous' ligands. In this work, promiscuous phage fusion proteins
were first identified by a novel selection scheme to enrich for pan-cancer cell
binding abilities, as indicated by conserved structural motifs identified
previously in other cancer types. Additionally, peptide sequences containing a
combination of motifs were identified to modulate binding. A panel of phage
fusion proteins was studied for their specificity and selectivity for lung and
pancreatic cancer cells. Phage displaying the fusion peptides GSLEEVSTL or
GEFDELMTM, the two predominate clones with greatest binding ability, were used to
modify preformed, doxorubicin-loaded, liposomes. These modified liposomes
increased cytotoxicity up to 8.1-fold in several cancer cell lines when compared
with unmodified liposomal doxorubicin. Taken together, these data indicate that
promiscuous phage proteins, selected against different cancer cell lines, can be
used as targeting ligands for treatment of heterogeneous tumor populations.
|*Molecular Targeted Therapy
[MESH]
|*Peptide Library
[MESH]
|Amino Acid Motifs
[MESH]
|Amino Acid Sequence
[MESH]
|Cell Line, Tumor
[MESH]
|Cloning, Molecular
[MESH]
|Doxorubicin/administration & dosage/therapeutic use
[MESH]
|Humans
[MESH]
|Intracellular Space/metabolism
[MESH]
|Ligands
[MESH]
|Liposomes
[MESH]
|Molecular Sequence Data
[MESH]
|Recombinant Fusion Proteins/chemistry/genetics/*metabolism/*therapeutic use
[MESH]
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