Cancer is the second leading cause of death worldwide, just behind cardiovascular disease. Winning the cancer war is a never-ending mandatory task. Nanotechnology with the help of noble materials (e.g. gold nanoparticles, NPs) is a powerful and invisible weapon against cancer. It enables scientists to utilize the unique physical, chemical and optical properties that naturally occur at the nanoscale. Under a suitable light irradiation, NPs can generate an incredible amount of heat suitable to literally burn the tumor sites. Although there are more than 100 types of cancers, our project will focus the attention on gliomas: the most aggressive tumors with a median survival of approximately 20 months in patients who undergo total surgical resection, radio and chemotherapy. In this project, we propose an innovative approach based on the possibility to combine in a single gold nano-unit: therapy, targeting and detection. To this end, the sweet surface modified NPs can selectively recognize the cancer cells; the presence of a radio tracer enables the possibility to localize NPs in the human-body with very high precision, thanks to the computer tomography (CT) - positron emission tomography (PET) technology; the photo-thermal properties of gold NPs are used to burn (once-for-all) the tumor sites. The magnetic resonance (MR) thermometry allows measuring the temperature distribution under laser irradiation while performing both in-vitro and in-vivo experiments. The project has a strong multidisciplinary approach because is conceived in such a way that physics, nuclear medicine and oncology work hand to hand in order to persuade the same accomplishment: winning the cancer battle.
In our project the link between nanotechnology and nuclear medicine represents a new opportunity in the field of oncology and cancer treatments. By exploiting the unique optical and thermal properties of plasmonic NPs, capped with sugar based materials and functionalized with radiopharmaceutical drugs, we propose the realization of a novel and powerful weapon in the fight against cancer. Our methodology enables the possibility to selectively target cancer cells without affecting healthy tissues. This is possible thanks to the unique properties of gold NPs: size, shape and functionality [1]. The ultra-small size (20-30nm) helps to avoid immune recognition (they are too small to be seen); the shape (from spherical NPs to rod-like NPs) can promote the cellular internalization (uptake); the chemical and physical functionality is a key factor for bridging NPs with a recognition system (e.g. sugar) or for remotely controlling the temperature around NPs (e.g. by using bio-transparent light) [2]. In this research project the strong impact is represented by the fact that we attempt to functionalize the NPs surface with non-toxic materials which are selectively accepted by cancer cells [3]. To do so, we exploit the affinity between cancer and sugar. Therefore, by covering the surface of NPs with sugar based materials (e.g. glucosamine), we pave the way to specifically target cancer cells without affecting the healthy ones. Once in situ, NPs can be remotely thermal activated by exploiting the capability of plasmonic NPs to convert infrared light into heat. The selective and localized heating is used to burn (once-for-all) the tumor sites without (or minimally) affecting the surrounding tissue. Interestingly, herein, we can also exploit the extraordinary capability to visualize the NPs (from outside) thanks to the presence of a radio tracer. Indeed, a CT-PET (positron emission tomography- computed tomography) scan technique will generate well detailed images used to verify the presence of NPs in the tumor sites.
In vivo experiments will be performed on mice, previously implanted with tumor cells (glioma). Subcutaneous injection in mice with NPs conjugated with a radio tracer (e.g. 18F-FDG) enables the possibility to perform a tomographic characterization by means of a CT-PET scan. When dealing with hyperthermia based applications, real-time assessment of thermal damage is the key to therapeutic safety and efficiency of such procedures. The lack of suitable technological options to assess the temperature of a targeted site has limited the large-scale marketing of hyperthermia treatment and thermally controlled drug delivery protocols [4]. Breakthroughs in basic research are also expected if a noninvasive, accurate, sensitive, and robust thermometer is made available for probing cellular behaviors. Indeed, it is very hard to measure the local temperature in the human body while NPs are illuminated with an external light source [5]. In order to overcome this issue, we will use the magnetic resonance (MR) thermometry technique for measuring the temperature increase under a laser irradiation. From a basic knowledge standpoint, this is a very important step forward in comparison with previously reported studies on similar subjects [6]. In fact, we will be able to combine therapy, detection/visualization and quantification thanks to the: photo-thermal properties (therapy); presence of a radio tracer (detection/visualization) and MR thermometry (quantification). For the first time, the MR thermometry will be used for in vivo studies of plasmonic NPs, opening a new scenario for the utilization of nanotechnology based thermal therapies.
References
1. A. O. Govorov and H. H. Richardson, Nano Today 2 (1), 30-38 (2007).
2. X. Xie, J. Liao, X. Shao, Q. Li and Y. Lin, Scientific Reports 7 (1), 3827 (2017).
3. C. Pignanelli, D. Ma, M. Noel, J. Ropat, F. Mansour, C. Curran, S. Pupulin, K. Larocque, J. Wu, G. Liang, Y. Wang and S. Pandey, Scientific Reports 7 (1), 1105 (2017).
4. Y. Chen, M. Ge, R. Ali, H. Jiang, X. Huang and B. Qiu, BioMedical Engineering OnLine 17 (1), 39 (2018).
5. J. Joensen, J. H. Demmink, M. I. Johnson, V. V. Iversen, R. Á. B. Lopes-Martins and J. M. Bjordal, Photomedicine and Laser Surgery 29 (3), 145-153 (2011).
6. M. A. K. Abdelhalim and S. A. Abdelmottaleb Moussa, Saudi Journal of Biological Sciences 20 (2), 177-181 (2013).