# Co-Adjuvant Nanoparticles for Radiotherapy Treatments of Oncological Diseases
## 3 Nanoparticles in Radiotherapy
### Multicomponent Nanoscintillators for X-PDT
Figure 5: (**a**) Sketch of the hybrid nanoscintillator composed based on a chrysotile nanotube (NT) functionalized with and H2 TPPS4– porphyrin (Por*) as singlet oxygen photosensizer and PEO as stabilizer for colloidal dispersion (NT-PEO-Por*). (**b**) Outline of the photophysical process involved in the sensitization of singlet oxygen (\({}^{1}\)O\({}_{2}\)*) production upon irradiation with X-rays. Free electrons and holes generated by interaction with the ionizing radiation in the NT localize at an emissive state that transfers its energy to the photosensitizer molecules on the surface promoting their excited singlet state (S\({}_{1}\)*). Upon intersystem crossing (ISC), the energy is transferred from the photosensitizer triplet to the dispersed molecular oxygen in triplet ground-state \({}^{3}\)O\({}_{2}\), which is promoted to its excited singlet state. (**c**) Evaluation of cell metabolic activity by the MTT test on U-87 cells stained with 20, 40, and 60 \(\upmu\)g cm\({}^{-2}\) of NT-PEO-Por*. (**d**) Relative fraction of dead cells estimated by the Trypan blue cell exclusion assay on U-87 cells stained with 20 \(\upmu\)g cm\({}^{-2}\) of NT-PEO-Por* as a function of the nominal dose delivered. (**e**) Evaluation of cell metabolic activity by the MTT test on U-87 cells stained with 20 \(\upmu\)g cm\({}^{-2}\) of NT-PEO-Por* as a function of the nominal dose delivered. MTT assays and Trypan blue cell counting were performed in triplicate. Statistical analysis: two-way ANOVA, \(p<0.0001\)*******. Error bars are the standard deviations of the mean values calculated for five independent experiments. Reproduced with permission from _ACS Appl. Mater. Interfaces_ 2021, 13, 11 [149]. Metal-organic frameworks containing a heavy metal, such as Zr or Hf, have shown attractive scintillating performances; especially, MOF architecture can include high energy radiation interacting dense nodes linked through photosensitizer molecules for therapeutic and diagnosis applications [150; 151; 152]. A variation of the organic component allows for structural modifications useable to tailor the MOF properties quite easily, thus enabling the fabrication of molecular-size MOFs--based scintillators where organic dyes or therapeutics can be used as ligands interconnecting high Z NS. In this architecture, the proximity of NS and ligands enables the prompt activation of the ligands by energy transfer, after the interaction of ionizing radiation with the scintillators. The adaptability of these nanometric architectures has been exploited by [PERSON] et al. in [152] to create cutting edge Hf based scintillating MOF (nMOF) for simultaneous X-PDT and immunotherapy (Figure 6). The synergetic combination of radiotherapy and immunotherapy represents a step forward towards the extension of the applications of radiotherapy for both local and systemic tumor rejection, by positively reducing the high-dose related RT toxicity. Figure 6: (**a**) Schematic illustration of the mechanisms of X-ray-induced RT-RDT by MOF nanocrystals. (**b**) Structure models of Hf\({}_{12}\)/Zr\({}_{12}\) secondary building units (SBUs), and 5,15-di(_p_-benzoate)porphyrin-Hf (DBP-Hf), 5,15-di(_p_-benzoate)porphyrin-Zr (DBP-Zr) and 2,5-di(_p_-benzoate)aniline- Hf (DBA-Hf) MOFs nanocrystals. (**c**) Structure models of Hf\({}_{6}\)/Zr\({}_{6}\) SBUs, and TBP-Hf and TBP-Zr nMOFs. (**d**,**e**) Transmission electron microscopy images of DBP-Hf (**d**) and TBP-Hf (**e**). The nMOF syntheses were repeated more than 20 times in each case and the particle morphologies and sizes were similar. (**f**,**g**) \({}^{1}\)O\({}_{2}\) generation of DBP-Hf (**f**) and TBP-Hf (**g**) upon X-ray irradiation (225 kVp, 13 mA), as determined by 4-nitroos-N,N-dimethylaniline assay. For DBP-Hf, the change in optical density (\(\Delta\)OD) at 439 nm is linearly fitted against the product of MOFs concentration (\(\mu\)M) and X-ray dose (Gy). For DBP-Hf or TBP-Hf samples irradiated with 10 Gy at Hf concentrations of 10 uM, two independent experiments were performed, and similar results were obtained.