# Co-Adjuvant Nanoparticles for Radiotherapy Treatments of Oncological Diseases
## 3 Nanoparticles in Radiotherapy
### Passive Nanoparticles as Enhancers of Energy Deposition in RT
In addition to its well-known application as contrast agent in MRI, recently the additional role of gadolinium nanostructures in RT has been modeled by computational analysis. Modeling results reveal the capability of Gd NPs at increasing the final delivered dose to the tumors site and the suitability in brachytherapy applications [97; 98]. Moreover, studies on gadolinium-NPs, namely AGuIX, confirm the occurrence of sensitization under ionizing radiation in vitro assay on HeLa cells, revealing the attractiveness of gadolinium-based NPs as alternative to  
Figure 3: (**a–c**) Radiation enhancement effect of 14 nm citrate-capped gold nanoparticles (AuNPs). (**a**) AuNPs improve the cell-killing effects of X-rays and fast carbon ions. (**b**) AuNPs improve the hydroxyl radical production of X-rays (assessed by 3-CCA). (**c**) AuNPs improve the hydroxyl radical production of carbon ions (assessed by 3-CCA). Reproduced with permission from Ref. [92]. Copyright Elsevier 2015.  
the widely used gold NPs for improving the efficacy of radiation cancer treatments [99].The use of platinum (Pt, Z = 78) NPs (PtNPs) as promising radiation sensitizers in radiotherapy cancer treatment has come into light in a small number of works with respect to the Au and Gd NPs. For instance, in 2010, it has been examined the case of platinum nanoparticles upon irradiation by fast carbon ions (LET = 13.4 keV \(\upmu\)m\({}^{-1}\)). Their use enables the strong enhancement of the biological efficiency of ionizing radiations and the amplification of tumor cells DNA lethal damage (single strand breaks, and mostly double strand breaks) induced by irradiation; moreover, formation of radicals in PtNP proximity has been proved to further contribute to the DNA strand breaks [100]. More recently, porous Pt NPs have opened the way for novel therapeutic strategies. Indeed, while promoting radiation induced cell cycle arrest by an effective energy deposition within the cancer cells, porous Pt systems enable also to generate oxygens (O\({}_{2}\)) from hydrogen peroxides (H\({}_{2}\)O\({}_{2}\)). The final outcomes of exploiting porous Pt NPs are the formation of DNA breaks with the generation of ROS and, at the same time, the hampering of the establishment of hypoxia condition in the tumor, being one of the major causes of cancer radioresistance [101]. Metal oxides nanoparticles are considered an alternative to full metallic systems. Hafraium oxide (hafnia, HfO\({}_{2}\)) has been considered in RT as sensitizer to increase energy dose deposit within cancer cells, owing to its high atomic number, electron density, and chemical stability. Hafraium (Z = 72) oxide nanoparticles (NBTXR3) have been designed in terms of size, surface charge, and shape, to concentrate in tumor cells to achieve intracellular high-energy dose deposit with reduced health hazards. Monte Carlo simulation considering a high-energy source of a few MeV predicts an enhancement of local energy deposit, within and close to the tumors where NPs are located, almost 9 times larger with respect to RT alone. In vitro and in vivo studies on the HT1080 fibrosarcoma cell line with NBTXR3 nanoparticles with high-energy sources confirm the results of the simulation, denoting a higher radio-induced cancer cell destruction rate in presence of high Z NPs [102]. Another recently discovered effect of NBTXR3 marks their ability to impact on the activation of the antitumor immune-response, open the way for their use in radio-immunotherapy [103]. Other interesting high Z materials enabling strong absorption of X-rays, are tantalum pentoxide (Ta\({}_{2}\)O\({}_{5}\)) NPs and bismuth oxide nanoparticles--Bi\({}_{2}\)Se\({}_{3}\), Bi\({}_{2}\)S\({}_{3}\), and Bi\({}_{2}\)O\({}_{3}\), the latter showing a multiplicity of characteristics for multimodal imaging, radiosensitization, as well as in radioprotection [81].