Study of a PEGylated-Protein G as a tool for on-demand targeted liposomes

We are presenting a drug delivery technology that can be directed on demand to varied types of tumors. The idea builds upon preliminary data published by Prof Pasut’s research group showing that the non-covalent interaction between a targeting antibody and a drug-tagged antibody-binding protein can be exploited to create versatile systems in which the antibody can be replaced depending on the target or tumor to be treated. To optimize this platform further, we intended to present the antibody-binding protein on the surface of doxorubicin-loaded liposomes and, then, depending on the type of tumor, add an antibody of choice to the system allowing its complexation with the protein and the formation of antibody-coated liposomes directed toward the intended target. In this proof-of-concept study, we used recombinant streptococcal protein G and exploited its affinity towards the Fc (fragment, crystallizable) moiety of immunoglobulins. We used trastuzumab, an anti-HER-2 positive breast cancer antibody, as a reference monoclonal antibody and, to achieve a higher potency, the antibody-drug conjugate Kadcyla. The main challenge of the proposed platform is the protein’s affinity towards the antibody, and its ability to maintain a stable complex until the construct reaches the target. This work covers the first steps in the presented topic focusing on the characterization of the non-covalent complexes. We believe that this system would contribute to the drug delivery field and bring us a step closer to a more accessible targeted delivery.