# Co-Adjuvant Nanoparticles for Radiotherapy Treatments of Oncological Diseases
## 3 Nanoparticles in Radiotherapy
### Multicomponent Nanoscintillators for X-PDT  
The attempt of finding oncological cures alternative to surgery, chemotherapy and radiotherapy relies on the use of selective and non-invasive approaches with reduced side effects. In the previous paragraph, we mentioned at the advent of PDT as FDA approved oncological treatment, which has been proposed as alternative to the RT for the treatment of primary tumors of skin, esophagus and lung. Far from being an exhaustive explanation, in brief, PDT principle is based on photoexcitation of a PS (among which we can mention noble metal complexes, metal organic frameworks, metal oxides or carbon-based nanostructures, as well as polymeric PS and small organic moieties [127]) to locally generate ROS species and cause cancer cells death. After interaction with light, the PS is excited from ground state (S\({}_{0}\)) to unstable singlet excited states. In particular, the first excited state (S\({}_{1}\)) may undergo intersystem crossing (ISC) to form a more stable excited triplet state (T\({}_{1}\)) with longer lifetime (\(\approx\)us). Triplet state of PS can produce ROS by interacting with water and molecular oxygen. The first interaction generates free radicals (type I), while the second one produces singlet oxygen moieties (type II). However, the most common PSs can be excited by UV/Vis light; in this wavelengths range light is reflected and scattered by the human tissues, rendering the PDT ineffective for deep-tissue treatment [128]. Moreover, PDT painful side effects can appear immediately after treatment as well as after months. In the literature, many research studies have been reviewing in detail the PDT processes, the advantages and limitations, together with the PSs guideline, for instance see refs [129; 130; 131; 132; 133]. One possible solution relies on the so-called second-generation photosensitizers showing higher molar extinction coefficient in the near-infrared region where biological tissues present a transparency window [134; 135]. Thanks to their high penetrability, X-rays offer another solution for adapting the PDT principle to deep tumors. From the first decades of the last century extensive studies have displayed the activation of the PS under ionizing radiation [136; 137]. Recently, an extensive review by [PERSON] et al. has offered an overview on the efficacy of X-rays in enhancing the toxic activity of some PSs, like hematoporphyrin derivatives, protoporphyrins, or metalloporphyrins They have listed the available photosensitizers used as radiosensitizers or as precursors of PDT effects in combination with radiation therapy [138]. A step forward in the progress of alternative therapies is provided by the so-called X-PDT. The strategy counts on the employment of scintillating nanoparticles (nanoscintillator;NS), able to convert the ionizing radiations into ultraviolet or visible light through a three stage scintillation process consisting in-conversion, transport, and luminescence [139; 140]. NS can be embedded in a biological surrounding, where both the absorption of X-rays by the NS and the deposition of energy by the exciting beam (or the following secondary particles) in its proximity can occur. Afterwards, NS can emit fluorescence (Figure 4a), alternatively, when NS is embedded in biological environment with other elements (organic dyes and therapeutics, for example), the energy can be transferred to the secondary moieties through multiple radiative emission/reabsorption process and/or through efficient energy transfer mechanisms (ET). The interaction can occur between the high-energy beam and the aqueous environment with the consequent excitation of the NS and then the activation of organics nearby (ET\({}^{\prime}\)); or the NS can directly absorb the X-rays and transfer the energy to the dye (ET\({}^{\prime\prime}\)). Lastly, also the organic molecules can interact with the primary beam by themselves (ET\({}^{\prime\prime\prime}\)) (Figure 4b). In X-PDT, high \(Z\) and dense NS are designed to be grafted by a PS therapeutic agent (Figure 4c).