Peptide-based nanoparticles for targeted delivery of Fluorescent Biosensors for Non-invasive in vivo Diagnostics – NANOSCREEN

The success of biotherapies requires efficient but selective delivery of therapeutic molecules to their target site and their internalization into malignant cells. Therefore, it is necessary to identify appropriate targets within pathological cells and to devise strategies for efficient and targeted delivery of drugs. Moreover it is essential to visualize and monitor biological activities in healthy and pathological cells, in order to design efficient and specific screening approaches to target alterations associated with development and progression of disease. Unfortunately, there is a general lack of technology for rapid in cellulo screening of potential drug compounds and for detection of biomarkers, which is essentially related to their intracellular localization. Currently used technologies for probing intracellular biomarkers and monitoring response to drugs are invasive, relying on cell lyses/fixation, lengthy and indirect. The general lack of strategy to probe targets in pathological cells calls for direct and sensitive means of tracing their levels and activities together with the development of strategies to mediate efficient intracellular delivery and improve targeting to the appropriate subcellular compartments. Therefore the development of potent delivery systems has become a major piece of the therapeutic puzzle and the success of non invasive cancer drug screening requires suitable carriers to deliver fluorescently labelled biosensors/bioprobes specifically to their target site.
Recently, we have developed a new strategy for small molecule and large protein delivery, based on small amphipathic peptides that form stable nanoparticles. NANOVEPEP technology is highly efficient for protein and antibody delivery in cellulo and in vivo. As such, this programme will aim to develop sensitive and non-invasive strategies to detect cell cycle regulators associated with cancer cell proliferation, thanks to fluorescent biosensors designed to recognize specific molecular or protein/protein interfaces, and combined with original nanoparticle carriers optimized to introduce these biosensors into cancer.
The aim of the program NANOSCREEN will be to establish a proof-of-concept that our technology meets the requirements for cancer drug screening applications. The major goal of this program will be to elaborate multifunctional peptide-based nanoparticles for efficient targeted delivery of small and large molecule bioprobes in cellulo that can be applied both as screening tools and for diagnostic approaches. For this purpose, the nanovector system NANOVEPEP will be optimized and functionalized in order to specifically target small molecule substrates, interface peptides and large antibodies into cells and to evaluate their potency as cancer drug screening tools. It will be divided into three major parts: (1) the optimization of stable and reproducible multifunctional peptide-based nanoparticles for the delivery of bioprobes for screening, (2) the characterization of the physico-chemical and structural features that control NANOVEPEP complex efficiency, (3) proof of concept of the potency of the NANOVEPEP particles for in situ cancer drug screening approaches on malignant cells using either interface peptides biosensors or subtracts for Tag-lyte technology coupled with homogeneous time-resolved fluorescence.
NANOSCREEN program will have a significant impact on life sciences, medical and technological applications. Technological innovations will include (1) the development of original and functionalized peptide-based nanoparticles for in cellulo delivery of biosensor/bioprobe as well as the development of original, fluorescence-based modular biosensors for in cellulo rapid screening of new specific drugs. The success of this project will contribute to early detection of active new anti cancer drugs in living cells in a non invasive fashion which will have a major incidence on future therapeutic developments