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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - CARTHER (Carbon-based nano-materials for theranostic application)

Teaser

Summary

Novel nanomaterials are considered to be of great strategic importance for the development of nanomedicine in Europe on a long-term basis. In particular, there is an enormously growing interest in research and development of IVth group nanostructures for various applications in the fields of bio-photonics as well as in the nanomedicine. Recent research indicates that carbon-based nanoparticles can penetrate into cells and can be used as luminescent labels due to the unique room temperature light emission. In addition, the unique physical properties of nanoparticles like cavitation, hyperthermia or formation of singlet oxygen can be used for the pioneering cancer therapy. The main general objective of our project aim creation of innovative approaches for multi-functional application of carbon nanomaterials for diagnostics and therapy of cancer. The combination of pre-clinical, in-vitro and in-vivo application of new photo-induced theranostic approaches based on carbon nanomaterials make this project a unique endeavor. More specifically, 4 different carbon nanomaterials, such as: carbon fluoroxide nanoparticles, nanodiamonds, carbon nanotubes and graphene developed by the partners involved in the project will be in focus of the proposed study. After their incorporation into cancer cell cultures and animals, original photo-induced imaging approaches (based on photo-electric and photo-acoustic measurements) will be applied. For the imaging purpose, the carbon nanomaterials will play a role of photo-sensitive nano-agents allowing efficient visualization (at minimal exciting optical powers) of the cells and tissues in which they will be incorporated. After identification and characterization, cancer cells and tumor tissues with enhanced content of the nano-carbon agents (compared to control cell and tissue samples) are planned to be selectively destroyed by photo-induced treatments due to simultaneously acting photo-induced thermal and acoustic effects. The cancer killing will be carried out by means of the same optical equipment (at optical powers above a characteristic threshold) previously applied for imaging purpose.

Work performed

During the period 01/01/2016 - 31/12/2017, protocols for reproducible fabrication of carbon nanomaterias and their stable dispersions in water have been developed (WP2) with participation of all the partners. Various reliable chemical procedures for surface functionalization of the carbon nanomaterials have been also developed (WP2). Characterization of physico-chemical properties of the fabricated and chemically functionalized carbon nanomaterials has been systematically carried out (WP2). Trainings devoted to: (i) electrochemical synthesis of carbon fluoroxide nanoparticles and their stable colloidal dispersion in aqueous solutions, (ii) preparation of stable dispersions of the carbon nanotubes and graphene in water, (iii) synthesis of nanodiamonds by various methods, (iv) surface chemistry analysis of the as-prepared carbon nanomaterials were carried out by all the partners. A special training has been organized by INSA Lyon for study of carbon nanomaterials impact on cell uptake and proliferation (WP3). Joint researches between the partners have been carried out in order to find suitable chemical procedures ensuring appropriate chemical functionalization of the carbon nanomaterials to guarantee their low cytotoxicity and efficient uptake by cell cultures (WP3). A systematic study on impact of the carbon nanomaterials on cell proliferation and differentiation has been performed under scientific coordination of INSA Lyon (WP3). In particular, some CFO, nanodiamond and graphene oxide samples have been found to be quite efficient to stop the proliferation of cancer cells. At the present time, it appears that the most appropriate nanoparticle for theranostic application are the nanodiamonds. Indeed, CFO nanoparticles have numerous advantages but the main problem is to secure their upscale production. Nanodiamonds can be either toxic (ND W-RT3D) or not toxic for cells (ND W-RT-5D), both cases can be usefull for example by applying ultrasounds after expsure of cells to initially non-toxic nanodiamonds.
In the frame of Work Package 4 started in July 2017, two trainings courses have been developped and carried out by Science Park on basic configurations of photo-electric and photo-acoustic measurements for their bio-imaging application. Two experimental set-ups allowing photo-electric and photo-acoustic measurements have been transfered to and built up at INSA Lyon by ukrainian researches from Science Park.

Final results

Progress beyond the state of the art:
1) Carbon fluoroxide nanoparticles originally synthesized by researches from INSA Lyon and nanodiamonds with specific surface chemistry developped by Ray Techniques company have been found to be the most efficient for incorporation into living cells.
2) An original experimental set-up for multi-modal (optical, photo-electric and photo-acoustic) bio-imaging purpose has been co-developped by researches from INSA Lyon and Science Park.
3) New and original method and system has been developed by researchers from RT & Aston U for industrial manufacturing of nanodiamond powder.
Expected results until the end of the project:
In future, joint researches between all the partners will be carried out in order to determine the most appropriate photo-excitation conditions for in-vitro cancer cell destruction. A special study will be performed in order: (i) to study physiologic effects of nano-carbon injections in mouse for determination of safety doses; (ii) to implant tumor in mouse model (AT84 cell line in C3H mouse), (iii) to check efficiency and reproducibility of tumor development, (iv) to treat the animals with carbon nanomaterials (with subcutaneous and intravenous treatments), (v) to check intratumoral localisation of the carbon nanomaterials by means of previously developped photo-acoustic imaging and to destroy in-vivo tumor sites labelled with the carbon nanomaterials by a photo-induced treatment.
Potential impact:
Cancer represents the second most important cause of death and morbidity in Europe. The multi-disciplinary researches epitomized in frames of our project is one of the European opportunities to catalyze scientific developments around nanotechnologies devoted to cancer treatment. Physicists, chemists and biologists from university and industrial sectors are teaming up in frame of this proposal to try to attack the cancer malignancies using original bio-functionalized carbon nanomaterials. The outcome of the project will represent new possible photo-induced cancer therapy approaches based on carbon nanomaterials. Market survey indicates that a big market opportunity for the bio-medical applications of the carbon-based nanomaterials remains open. European/International companies will benefit from the technologies developed within the CARTHER proposal due to the novel nanomaterials, especially nanodiamonds and carbon fluoroxide nanoparticles. The proposed novel cancer therapy strategies have a considerable potential for reducing the direct and indirect healthcare costs and increasing cancer therapy efficiency. Profit could result through the â€œeconomyâ€ generated by an earlier diagnosis of disease relapse and treatment. If our carbon nanomaterials prove to have a higher efficacy in comparison with the current standard-of-care, a new market product will be clearly foreseeable.