Cytotoxic tumor targeting with scFv antibody-modified liposomes
Related Experiment Video
Updated: Aug 20, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Cornelia Marty1, Reto A Schwendener
1Molecular Cell Biology, Paul Scherrer Institute, Villigen, Switzerland.
Abstract:
Specific targeting of liposome-formulated cytotoxic drugs or antigens to receptors expressed selectively on target cells represents an effective strategy for increasing the pharmacological efficacy of the delivered molecules. We have developed a feasible technique to selectively attach antibodies and fragments thereof, but also small-mol-wt ligands such as peptides, carbohydrates, or any molecules that recognize and bind target antigens or receptors to the surface of small unilamellar liposomes. Our concept is based on the site-specific functionalization of the ligands to be attached to the liposomes by thiol groups. These thiol groups can easily be introduced to antibodies or peptides by addition of cysteines, preferably at sites that do not interfere with the receptor binding domains. Optimally, the site-specific modification is introduced at the C-terminal end of the ligand, separated by an inert spacer sequence located between the thiols and the specific part of the ligand. The thiol-reactive molecules on the liposome surface are maleimides that are linked to phospholipids composing the liposome bilayer membrane. We illustrate the coupling method of a functionalized single-chain antibody fragment with binding specificity to ED-B fibronectin, an isoform of fibronectin exclusively expressed in tumor tissues, to long circulating small unilamellar poly(ethylene glycol) liposomes.
Insights
Researchers developed a method to attach targeting molecules, like antibodies, to liposomes for precise drug delivery. This technique enhances drug efficacy by targeting specific receptors on cells, particularly in tumor tissues.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- Targeted drug delivery using liposomes enhances therapeutic efficacy.
- Selective targeting of cancer cells is crucial for minimizing off-target effects.
- Liposome functionalization allows for specific binding to cellular receptors.
Purpose of the Study:
- To develop a versatile method for site-specific attachment of ligands to liposomes.
- To enable targeted delivery of drugs or antigens to specific cell populations.
- To demonstrate the feasibility of this technique using an antibody fragment targeting tumor-specific fibronectin.
Main Methods:
- Site-specific functionalization of ligands (antibodies, peptides) with thiol groups.
- Introduction of thiol groups via cysteine addition, preferably at the C-terminus with a spacer.
- Attachment of thiol-functionalized ligands to maleimide-modified liposomes.
- Utilizing poly(ethylene glycol) (PEG) liposomes for enhanced circulation time.
- Coupling of a single-chain antibody fragment (scFv) specific to tumor-associated ED-B fibronectin.
Main Results:
- A robust and feasible method for ligand-liposome conjugation was established.
- Site-specific attachment ensures that ligand binding domains remain functional.
- Demonstrated successful conjugation of an ED-B fibronectin-specific scFv to PEG-liposomes.
- The developed liposomes show potential for targeted delivery to tumor tissues.
Conclusions:
- The developed method allows for precise and efficient functionalization of liposomes with targeting ligands.
- This approach significantly advances targeted drug delivery strategies for cancer therapy.
- Site-specific conjugation is key to maintaining the biological activity of targeting molecules.
