A novel generation of Affitins for targeting cancer cells with drug-loaded nanocapsules
(2017)
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- Abstract
- A progressive strategy against cancer is the targeting of tumour-associated antigens by specific ligands coupled to nanoparticles, carrying therapeutic or imaging agents. Antibodies are the most widely used targeting molecules, but they possess limitations as high production costs, complex structure and limited stability. Affitins are highly stable engineered affinity proteins, derived originally from Sac7d, an archaeal polypeptide from the 7 kDa DNA-binding family (also known as Sul7d family). These binders show comparable affinity and specificity to those of antibodies, while being thermally and chemically more stable, cheaper to produce, easier to engineer and present a simpler structure and 20-fold smaller size. Lipid nanocapsules (LNCs), prepared by solvent free process, possess great stability and high efficiency for lipophilic drugs encapsulation and protect the drug from rapid degradation. Targeting drug-LNC to cancer cells can further decrease drug concentration in normal tissues and lower the toxicity. The aim of the project is to combine the advantages of Affitins as targeting agents and LNCs as carriers in order to create vehicles for delivering payloads to cancer cells. The first goal of this work was to identify and characterize a shorter member, but still very stable, of the Sul7d family in order to further improve the affinity scaffold, and then to use it for the generation of Affitins, recognizing the tumour-associated Epithelial Cell Adhesion Molecule. The last goal was to attach the new binders as affinity moieties to LNCs and to assess the tumour targeting of these complexes.
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Citations
Kalichuk, V. (2017). A novel generation of Affitins for targeting cancer cells with drug-loaded nanocapsules. https://hdl.handle.net/2078.5/78768