Optimization of illumination in interstitial photodynamic therapy for high-grade brain tumors
Résumé
This work addresses the optimization issue of interstitial photodynamic therapy (iPDT) for high-grade brain tumors guided by real-time imaging. In this context, multifunctional nanoparticles, consisting of a surface-localized tumor vasculature targeting neuropilin-1 and encapsulated PDT and imaging agents, have been developed in previous works. Now, the problem is to determine the optimal therapeutic modalities, in particular the light dose to deliver, the position of the light fiber and the diffuser type. Indeed, these modalities depend on the light propagation (i.e. absorption and scattering of photons), which itself depends on the optical properties of the tissues, properties that are modified by the presence of the multifunctional nanoparticles. In this work, we first show that the nanoparticles with or without peptide grafts preserve the photophysical characteristics of the photosensitizer, essential to the iPDT effectiveness. The characterization of optical (absorption and scattering) coefficients in various biological tissues of different species exists in the literature. However, there are very few studies evaluating these coefficients in vivo, and let alone in presence of nanoparticules. So, we propose a method to estimate in vivo optical parameters of subcutaneous tumors (U87) grafted in nude mice with and without nanoparticles. We then show that the presence of nanoparticles in the tumor tissue influences significantly the optical coefficients, and so on, the light propagation. These results have used to simulate the light propagation in the tumor tissues according to different experimental conditions and have allowed to optimize the fiber position. Finally, these simulations have also demonstrated the importance of the light diffuser choice to treat a tumor whose diameter is greater than 2 mm.