Engineered Hormone Analogs as Functionalized Self-Assembled Nanoparticles

Talia Shekhter Zahavi, Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
Eyal Rub, Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
Yoseph Salitra, Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
Ludmila Buzhansky, Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
Ehud Gazit, Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel

Targeted drug delivery using decorated nanoparticles has a great potential in advanced therapy. Covalent conjugation is a common approach for the attachment of targeting agents to nanocarriers. Here we offer an alternative platform which incorporates well-studied peptide-based cancer targeting moiety together with self-assembling component. The hybrid bifunctional peptide combines tumor specificity together with an inherent ability to self-associate. We designed and synthesized peptide conjugates which possess three essential elements: minimal peptide self-association motif, a linker and a hormone-based targeting moiety. Diphenylalanine (FF), a key recognition module, was used in the hybrid molecule to induce the self-organization of the peptide into nanostructures and a hormone analogue was utilized as the cancer specific component. The conjugation of the FF motif to the bioactive peptide sequence resulted in the self-assembly of the engineered peptide into ordered nanostructures. Moreover, the FF-hormone analogue could co-assemble together with another FF-peptide (i.e., tert-butoxycarbonyl diphenylalanine) into nanospheres. Transmission electron microscopy, atomic forces microscopy and dynamic light scattering studies of the hybrid peptides revealed the formation of nanospheres in the average size range of 100-200 nm. We determined the ability of co-assembled nanospheres to encapsulate gold nanoparticles and fluorescein dye. Furthermore, the binding capacity of the hybrid assemblies to cancer cells was verified. Taken together, we provide a proof-of-principle for the induction of hormone association via the introduction of a simple dipeptide recognition motif to generate specific targeted nanostructures that can efficiently deliver theranostics to cancer cells.