Dou and colleagues used this type of nanoparticles for delivery of antipolo-like kinase 1 (Plk1, a kinase enzyme involved in cell division) siRNA to breast malignancy cells (22). drawback correlated with this type of antibodies is usually their large size, which may negatively impact their potency. Constant domains of antibodies are not directly involved in antigen acknowledgement and binding. Therefore, single-chain antibodies (scFvs), which are devoid of constant domains, are still able to bind their specific antigens (8,9). Because of their small size, scFvs are expected to display a higher cell penetration rate than their full-length counterparts; therefore, they are more favorable for use as targeting elements in drug delivery systems (10). This review includes the most updated studies regarding the use of scFvs as targeting elements of drug delivery systems and presents innovative strategies for increasing the efficiency of drug delivery systems, including liposomal and nonliposomal drug carriers. USE OF SCFV MOLECULES FOR SIRNA DELIVERY Efficient Delivery of siRNA to Breast Malignancy Cells Using (Arginine)9CAnti-HER2-scFv Fusion Peptide Small interfering RNAs (siRNAs), which interfere with expression of mRNA molecules, have gained enormous attention for malignancy treatment (11,12). A major drawback correlated with nontargeted siRNA delivery systems is the lack of specificity for the target cells. Jiang and colleagues used an anti-HER2-scFv antibody to specifically deliver siRNA molecules to TCS 401 HER2-overexpressing breast malignancy cells to suppress the expression of chemokine receptor 4 (CXCR4), a protein that plays a main role in cell survival and malignancy metastasis. The anti-HER2-scFv contained nine arginine residues at its C-terminal end (Physique 1A) (1). Arginine residues are widely used to deliver nucleic acids into cells; they act as a cell penetration peptide that binds the cells and transduces the siRNA molecules across the plasma membrane (Physique 1B) (13). The anti-HER2-scFv significantly increased the delivery of the siRNA molecules to HER2-positive BT-474 breast malignancy cells and tumor xenografts, while it was unable to deliver siRNA molecules to MDA-MB-231 cells and tumor xenografts. MDA-MB-231 cells do not express HER2 receptors on their surface, and as a result, anti-HER2-scFv molecules cannot identify them. Reduced tumor metastasis and prolonged animal survival have been the results of anti-HER2-scFv-mediated delivery of anti CXCR4-siRNAs to BT-474 xenograft-bearing mice (1). Open in a separate window Physique 1. Structure and action mechanism of scFv-arginine fusion peptide and scFv-based immunoliposome (IL). (A) Nine arginine residues act as a cell-penetrating peptide, which help the fusion peptide enter the cell. (B) Fusion peptide binds to a specific receptor on the target cell by its scFv moiety and enters the cell by its C-terminal tail arginine resides. (C) Cysteine residue at the C-terminal end allows the scFv to form a covalent bond with PEGCPLA nanoparticles to produce IL. (D) IL binds to the target cell through its scFv, becomes internalized into the cell and releases the encapsulated drugs. siRNA Delivery Using (Arginine)9-Anti-EGFR-scFv Fusion Peptide to Overcome Drug Resistance in Lung Malignancy Cells Epidermal growth factor receptor (EGFR) overexpression occurs in many types of human cancers including lung malignancy (14C16). Tyrosine kinase inhibitors (TKIs), which inhibit the tyrosine kinase activity of the EGFR intracellular domain name, can suppress malignancy progression. However, after a variable period of time, patients acquire resistance to such inhibitors for several reasons, including point TCS 401 mutations in the EGFR intracellular tyrosine kinase domain name which annuls the binding of TKI to EGFR, mutation and subsequent activation of Kirsten rat sarcoma viral oncogene (KRAS), epithelial-to-mesenchymal transformation, gene amplification TCS 401 of mesenchymal-to-epithelial transformation (MET) factor and so forth (17C20). To overcome TKI resistance in lung malignancy, Lu and colleagues produced a single-chain format of nimotuzumab, an anti-EGFR monoclonal antibody, and used it to specifically deliver siRNA molecules to EGFR-expressing cells to suppress and gene expression (21). The scFv contained nine additional arginine residues (9R) at its C-terminal end that guaranteed the penetration of fusion peptide (scFv-9R), and therefore delivery of siRNAs, into EGFR-positive cells. Control scFvs, which were devoid of C-terminal 9R, were Rabbit Polyclonal to PLG unable to deliver siRNA molecules. siRNA molecules were loaded on TCS 401 scFv molecules by simply combining, and not by covalent bonds..