Artikel
Single-chain Fv immunoliposomes for drug delivery in cancer therapy
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Autoren
Veröffentlicht: | 20. März 2006 |
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Gliederung
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Liposomes are versatile carrier systems for the delivery of cytotoxic drugs in tumor therapy. Liposomes have the advantage to protect the encapsulated drug from degradation and elimination and to improve its pharmacokinetic properties. Active tumor targeting can be achieved by incorporating tumor-specific ligands such as peptides or antibodies into the liposome surface. We have developed immunoliposomes based on recombinant single-chain Fv fragments (scFv) genetically modified to allow for a site-directed coupling through a C-terminal cysteine residue. These scFv’ fragments can be expressed in bacteria in sufficient quantities. Coupling to liposomes is achieved by incorporating functionalized lipids (e.g. maleimide-PEG-PE) into the lipid bilayer. Using various scFv fragments directed against proteins expressed by proliferating endothelial cells (endoglin), tumor stroma fibroblasts (fibroblast activation protein) or tumor cells (e.g. CEA), we could demonstrate target cell specific binding and uptake of these immunoliposomes in vitro. Initial studies showed that these immunoliposomes are also able to selectively deliver cytotoxic drugs into target cells and to increase cytotoxicity. Thus, these immunoliposomes represent promising carrier system for efficient delivery of high payloads of chemotherapeutic drugs or other molecules to target cells.
References
- 1.
- Kontermann RE. Immunoliposomes for cancer therapy. Curr Op Mol Ther. in press. 2006.