Fluorescent Peptide Biosensors for Imaging Protein Kinases involved in Cell Proliferation and Cancer

Abstract

Cyclin‐dependant kinases play a central role in coordinating cell growth and division and in sustaining proliferation in many pathological conditions, thereby constituting established biomarkers of proliferation and attractive molecular targets for the development of anticancer drugs. Faced with the lack of diagnostic approaches to evaluate the relative levels of these intracellular biomarkers within tumours in a standardized fashion, we have developed peptide biosensors that recognize molecular interfaces specific to cyclin‐dependent kinases. Efficient delivery of biosensors into living cells was achieved thanks to nanoparticle formulations of cell‐penetrating peptide carriers (PEP & CAD family), thereby allowing for direct visualization of endogenous CDK‐cyclin complexes. Moreover, we developed a strategy for ratiometric quantification of CDK‐cyclin levels in different healthy and cancer‐derived cell lines, providing a means to monitor alterations in cyclin‐dependent kinases associated with tumoral progression. This technology can be further extended to probe other intracellular targets, thereby offering promising perspectives for development of non‐invasive diagnostic approaches.