Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells

Abstract

Liposomes functionalized with monoclonal antibodies or their antigen-binding fragments have attracted much attention as specific drug delivery devices for treatment of various diseases including cancer. The conjugation of antibodies to liposomes is usually achieved by covalent coupling using cross-linkers in a reaction that might adversely affect the characteristics of the final product. Here we present an alternative strategy for liposome functionalization: we created a recombinant Fab antibody fragment genetically fused on its C-terminus to the hydrophobic peptide derived from pulmonary surfactant protein D, which became inserted into the liposomal bilayer during liposomal preparation and anchored the Fab onto the liposome surface. The Fab-conjugated liposomes specifically recognized antigen-positive cells and efficiently delivered their cargo, the Alexa Fluor 647 dye, into target cells in vitro and in vivo. In conclusion, our approach offers the potential for straightforward development of nanomedicines functionalized with an antibody of choice without the need of harmful cross-linkers.

Development of therapeutic antibodies for the treatment of diseases

“…Antibody-engaged effector cell functions may enhance the therapeutic efficacy of bispecific antibodies. With regard to immunoliposomes, the binding site of the antibody (scFv or Fab) is cleaved from the constant region and subsequently conjugated to different nano-drug delivery systems, such as liposomal drugs, to provide more specific targeting [263, 264]. Lastly, CAR-T involves inserting the gene for a chimeric T cell receptor-antibody targeting a specific cancer marker into T cells, such that the engineered cells target and kill cancer cells [265, 266].…”

Antibody‐Incorporated Nanomedicines for Cancer Therapy

“…[343] The Fab-modified nanoparticles may display more controllable sizes, higher targeting efficiency, better tumor penetration, and enhanced efficacy. [344][345][346][347][348] Therefore, the applications of Fab-conjugated nanoparticulate systems have attracted great interest in cancer-targeted drug delivery. [345][346][347][348][349] For instance, Greene et al utilized a disulfide re-bridging technology to selectively insert strained alkyne handle-conjugated pyridazinedione moieties into the reduced disulfide bonds of non-engineered trastuzumab Fab fragments, for further conjugation with azide-terminated PLGA-PEG nanoparticles by the SPAAC reaction (Figure 8a,b).…”

Bio-Nanocarriers for Lung Cancer Management: Befriending the Barriers

“…The immunoliposomes containing the CD59 and CD48 FAbs were thus observed to have dual specificity. The Fab-labelled immunoliposomes were demonstrated to target the antigen-positive cells with great affinity and specificity [ 314 ]. The multimodal platform can be employed for the targeted delivery of several therapeutic and imaging agents to the cells overexpressing the receptors for these antibodies, like lung cancer [ 315 ].…”