We present a proof of concept for a new nanometric multiplex system inspired from peptide phage display technology [1] for discovery of molecules with biological activity using live cells or in vivo. The advantage of the new platform is that non-natural molecules such as D-peptides can be screened directly on cells of interest.
The new system consists of a library of biocompatible monodispersed nanohydrogels that can be modified with orthogonal fluorescent flags and carry molecules either natural or synthetic. The system can be panned on cell cultures or in vivo as mixtures for discovering molecules that bind or interact with target cells detected by flow-cytometry, microscopy or imaging.
The system is composed of Nanohydrogels (NHG's) carrying a panel of fluorescent probes such as FAM, TAMRA, CY5 and Cy7 or a combination of them for multiplexing, and molecules such as D-peptides, or synthetic small molecules attached covalently side by side with specific flags. Appropriate mixtures of these NHG's are incubated with cancer cells and affinity for these cells is observed using flowcytometry, microscopy or imaging. The new platform allowed the discovery of a number of D-peptides that target cervical, breast and prostate tumors.