Use of single chain antibody derivatives for targeted drug delivery

Abstract

Single chain antibodies (scFvs), which contain only the variable domains of full-length antibodies, are relatively small molecules that can be used for selective drug delivery. In this review, we display how scFv antibodies help improve the specificity and efficiency of drugs. Small interfering RNA (siRNA) delivery using scFv-drug fusion peptides, siRNA delivery using scFv-conjugated nanoparticles, targeted delivery using scFv-viral peptide- fusion proteins, use of scFv in fusion with cell penetrating peptides for effective targeted drug delivery, scFv-mediated targeted delivery of inorganic nanoparticles, scFv-mediated increase of tumor killing activity of granulocytes, use of scFv for tumor imaging, site-directed conjugation of scFv molecules to drug carrier systems, use of scFv to relieve pain, use of scFv for increasing drug loading efficiency are among the topics that are discussed here.

Keywords: Immunoliposome; fusion peptide; nanoparticle; scFv; targeted drug delivery.

Figure 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 PEG–PLA nanoparticles to create IL. (D) IL binds to the target cell through its scFv, becomes internalized into the cell and releases the encapsulated drugs.

Figure 2.

Schematic view of a siRNA-loaded immunoliposome (IL) and a short peptide–scFv fusion peptide. (A) scFv molecules bind to PEG particles on the surface of siRNA-loaded IL to form a targeted siRNA carrier. (B) Targeting ligand of the IL consists of a scFv molecule, a short linker, 10 histidine residues and a cysteine residue that involves in covalently binding to PEG particles. (C) Amino acid sequence of TKKTLRT forms a short peptide with cell penetration capacity. (D) This short peptide allows the fusion peptide to enter the target cells previously recognized by scFv moiety.

Figure 3.

Structure and/or functional mechanism of some scFv-based drug carriers. (A) Monovalent and bivalent formats of Ranpirnase–scFv fusion peptide. Ranpirnase and scFv are joined together with a linker peptide. (B) Schematic view of a doxorubicin-loaded bi-specific IL. The targeting ligand is a fusion peptide composed two scFv molecules, anti-FAP scFv and anti-CD105 scFv. (C) Deferoxamine (DFO)-loaded anti-FAP IL. Anti-FAP scFvs contain a cysteine residue in their linker region that makes a covalent bond with PEG molecules on the surface of liposomes. The resultant ILs are able to bind FAP proteins expressed on the surface of TGF β1-activated fibroblasts and reduce collagen deposition. (D) Adriamycin (ADM)-loaded scFv molecule. Dextran can serve as a linker for effectively loading ADM molecules on scFv molecules. (E) A nanodisk composed of reconstituted high-density lipoprotein particles and apo-AI–anti-CD20 scFv fusion peptide to specifically deliver curcumin to CD20-positive non-Hodgkins lymphoma (NHL) cells. The fusion peptide constitutes the protein scaffold of nanodisk and binds NHL cells through its scFv moiety. The structure of nanodisk has been derived from the work of Crosby and colleagues (71).