« Green » laser ablation-based synthesis of functional colloidal nanomaterials for cancer detection and therapy – LASERNANOBIO

This White program ANR project addresses the development of novel non-chemical routes to synthesize inorganic photosensitizers, contrast and vectoring agents for tasks of cancer imaging and treatment. Colloidal inorganic nanomaterials are now increasingly popular in cancer research due to extremely promising optical characteristics and a capability of targeting (vectoring) tumours based on their selective size accumulation (Enhanced Permeability and Retention effect). In particular, inorganic semiconductor-based quantum dots (QDs) can provide much better fluorescent characteristics compared to organics fluorophores, suggesting their efficient use as contrast agents in cancer imaging. In contrast, many nanomaterials are capable of generating singlet oxygen under photoexcitation, which makes them excellent candidates for Photodynamic therapy of cancer. However, the development of nanoparticle-based detection and therapy technologies is hindered by a relative toxicity of inorganic nanomaterials. In particular, even the use of biologically friendly nanomaterials (Si, TiO2, Au etc.) is accompanied by toxicity issues, since conventional chemical routes for their fabrication normally imply the use of many by-products remaining on the nanoparticle surface after the fabrication process and presenting residual toxicity.
Our project is aimed at the development of “green” laser-assisted methods for the synthesis of functionalized colloidal nanomaterials and the fabrication, on their basis, of novel non-toxic nanoparticle-based agents for tasks of cancer diagnostics and treatment. The proposed approach is based on a series of findings of project participants related to the development of methods for fs laser ablation in aqueous solutions, which make possible the production of nanomaterials with unique properties, including: (i) variable size and very weak size dispersion in the absence of chemical toxic reducers; (ii) unique surface chemistry, not reproducible by any other chemical route; (iii) possibility of controlling the surface composition by performing the ablation in the presence of appropriate functional groups. (iv) low selectivity to material of ablation, which enables to consider new materials for nanostructuring. In the frame of the project, we plan to continue the elaboration of the fs laser ablation procedure toward the synthesis of novel materials and complex structures. Si and its compounds will be considered as the basic material, since Si can provide interesting optical properties (fluorescence, singlet oxygen release), is biocompatible and biodegradable, while strategies of functionalization of silicon surface are elaborated. As alternative materials, we plan to use several other biocompatible semiconductors, metals and complex structures (alloys, core-shells etc). It is implied that the nanoparticles will be laser-synthesized, functionalized during or after the laser ablation procedure, and tested to determine structural and optical characteristics. Finally, we will run cancer cell uptake and cytotoxicity studies on the synthesized materials and carry out first “in vivo” tests (activity of Collaborator groups). The project will be accomplished by three partner laboratories from Mediterranean University: (1) “Lasers, Plasmas et Procédés Photoniques” (LP3, UMR6182 CNRS), (2) “Centre Interdisciplinaire de Nanoscience de Marseille” (CINaM, UPR3118 CNRS), and (3) “Centre de Recherche en Oncologie biologique et Oncopharmacologie (CRO2, UMR911 INSERM ) in Collaboration with 3 partner groups from USA, Germany and Russia. Such consortium will profit from interdisciplinary and complementary expertises of involved partners LP3 (photonics, material science), CINaM (surface and organic chemistry) and CRO2 (biology, medicine). It is expected that the laser-synthesized colloidal materials will be much less toxic and provide superior characteristics compared to existing contrast agents and photosensitizers