GoldenEye

The aim of this project is to propose an innovative approach based on specifically designed gold nanoprobes for imaging and hyperthermia in Renal Cell Carcinoma (RCC). These nanoparticles will serve both as powerful contrast agent for enhanced photoacoustic imaging and as efficient heat sources for local tumor thermal destruction. The microvessel network of malignant tumors offers a preferential area of distribution and enhanced uptake for nanoparticles, and RCC is particularly well suited since it is one of the most highly vascularised human tumor with a high metastatic potential through blood vessels. The originality and ambition of the project is to use the unique optical properties of gold nanorods and nanoshells for a fine in vivo characterization of the microvessel network of malignant tumors, and for the local photothermia of targeted tumor areas. This is a rupture with already clinically validated methods of in vivo tumor imaging which are based on the volume assessment of the tumoral mass, or on its capacity to fix markers of the tumor cell metabolism. Besides, a major problem for the in vivo human cancer imaging is the lack of precise assessment of the tumoral microvessel network. This assessment is particularly important for the follow up of cancers treated with new antiangiogenic drugs. We propose to fill these gaps by pursing the following aims: A. investigate the efficiency of nanoparticle (NP) retention for NP enabled plasmonic photothermal therapy in a unique xenograft mouse model; B. develop the techniques of interstitial fluence rate/autofluorescence measurements and photoacoustic imaging to quickly and directly monitor the outcome of plasmonic photothermal therapy; C. demonstrate that these two techniques are complementary for the monitoring of plasmonic photothermal therapy in terms of optical contrast, penetration depth and spatial resolution. The proposed research will yield several outcomes that may have significant clinical and/or scientific impacts: A. Nanotechnology enabled plasmonic photothermal therapy will provide a minimally invasive alternative to current cancer therapies for treating RCC. B. The optical techniques developed in this project will be extremely useful for the monitoring of cancer therapy and noninvasive characterization of microvasculature in deep tissue in both clinical applications and biological research. C. The xenograft mice model for RCC will provide an alternative of human RCC for medical research to ameliorate the problem of insufficient human tissues for medical research. The project uses highly specialized technologies and methodologies already developed and mastered by the physicists, physicians and biologists partners of the consortium: plasmonic properties of the gold nanoprobes, in vivo optical tomography techniques, xenografts of human tumors, assessment of therapy-induced tissue damage and plasmonic hyperthermia. The complementarity of the french and singapore partners is essential for the success of the project. Singapore team will be in charge of the plasmonic photothermal therapy and autofluorescence sensing, the french partners will develop nanoplasmonic enhanced photoacoustic imaging and preclinical mouse model of the RCC. For the final task of the project, all the partners will work together jointly in a unique place at the Hospital Saint Louis to investigate the effects of plasmonic photoheating using non invasive photoacoustic imaging on the preclinical mouse model.