# Co-Adjuvant Nanoparticles for Radiotherapy Treatments of Oncological Diseases
## 3 Nanoparticles in Radiotherapy
### Multicomponent Nanoscintillators for X-PDT
In order to employ energy transfer from the NS to the PS for triggering the ROS and \({}^{1}\)O\({}_{2}\) production, the PS absorption spectrum should be resonant with the NS emission. Potentially, the exploitation of X-rays and heavy NS fulfills all the constraints for RT applications and for inducing radiosensitization (Section 3.1); at the same time, the use of PS, mostly \({}^{1}\)O\({}_{2}\) producing PS, being attested to be more efficient in the killing of malignant biological tissues and cells [127], guarantees an additional cytotoxicity towards the cancer cells destruction, mimic the action of the traditional PDT. The outcome of the RT- and PDT coupling remains unclear: besides the concept that the final result is just a sum of the effects from the two individual therapies, it has been demonstrated that X-PDT can produce important synergetic effects resulting in an improved efficiency in killing the tumor cells and in the overall reduction of the total dose to the patient [18]. Many inorganic nanomaterials like oxides, fluorides, silica-based nanostructures and semiconductor nanocrystals have been combined with organic photosensizers towards X-PDT applications [141; 142; 143; 144; 145; 146; 147; 148]. We can consider, for instance the case of silica-based nanotubes coupled to PS, displaying noteworthy therapeutic effects thanks to the synergy between RT and PDT [149]. Previous studies have proved the low toxicity of stoichiometric chrysotile [Mg\({}_{3}\)(Si\({}_{2}\)O\({}_{5}\))(OH)\({}_{4}\)] nanotubes featuring also the ability to pass the blood brain barrier, potentially important in cancer brain treatments [58]. Thanks to their density, chrysotile nanotubes have been proven to respond to X-ray irradiation by emitting light in the blue  
Figure 4: Sketch of the working principle of X-ray activated X-PDT. (**a**) Inorganic nanoscintillators (NS) can be easily embedded in a biological surrounding. (**b**) The NS scintillation luminescence can be exploited to excite a secondary photoactive moiety (dye) by energy transfer (ET). (**c**) Multicomponent hybrid nanosystems can be fabricated by decorating the NS surfaces with specific photoactive functionalities, for example PDT agents, whose action is sensitized by ET from the NS that mainly interacts with the ionizing radiation. wavelength range, suitable to excite meso-tetra(4-sulfonatophenyl) porphyrin (H2 TPPS4-) as PS. Thus, the surface of chrysotile scintillating nanotubes has been functionalized by an ionic self-assembly strategy with this efficient PS, able to produce singlet oxygen toxic species upon photoexcitation (Figure 5a). The study of luminescence behavior under X-rays (RL) and light (PL) excitations discloses the occurrence of a fast energy transfer (in ps range) from the chrysotile to the PS, together with the sensitization of singlet oxygen production upon ionizing radiation (Figure 5b). As expected, also bare nanotubes enable a sensitization of the \({}^{1}\)O\({}_{2}\) under ionizing radiation, due to the enhancement in energy deposition in presence of elements with higher \(Z\) than the surrounding biological medium. A further stabilization of the functionalized nanotubes has been obtained by covering their surface with polymeric shell. This ultimate composition boosts the ability of the NS to enhance the production of singlet oxygen in an aqueous environment by ET mechanism to PS under X-ray irradiation. Tests in vitro--mimic the radiotherapy dose depositions--show that stabilized chrysotile nanosystems functionalized with porphyrins enable to sensitize the singlet oxygen species at the lowest doses thanks to the contribution of a high-density material, and the effective toxic action of PSs activated by the nanoscintillators (Figure 5c,d). This opens the possibility of effectively reducing the high-energy radiation exposure of patients during oncological therapies.