# Co-Adjuvant Nanoparticles for Radiotherapy Treatments of Oncological Diseases
## 5 Targeting Strategies for Enhancing NPs Sensitizing Effects
An alternative is represented by the aptamers that are attractive for in vivo visualization, as they can couple some diagnostic agents, such as fluorescent or radionuclide labels, bioconyjugates and nanopar  
Figure 8: Schematic illustration of the functionalization process of bovine serum albumin (BSA) gold nanoclusters (AuNCs) with folic acid and Herreeptin and the mechanism of cellular internalization by binding with folate and human epidermal growth factor 2 receptors on the surface of SK-BR3 cells. Reproduced from _European Journal of Pharmaceutical Sciences_**2020**, 153, 105487. [179] Copyright Elsevier 2020.  
therapeutic agents and as sensitizers in RT, especially for brain tumors [181; 182]. Aptamer functionalized metal oxides and metals containing nanostructures have been proposed for tumor-targeted delivery and efficient PDT treatment [183; 184]. ZnO catalyst NPs have been studied for targeted PDT therapy in combination with chemotherapy by loading the NPs with anti-cancer drugs. The results presented in [184] show an enhanced cellular uptake of the NPs and they validate the successful therapeutic cytotoxic effect with a higher rate of death of cancer cells, if compared to the one of single photo--or chemotherapy. In spite of the significant advancements made in targeting strategies of NPs, potential harmful effects may occur depending on the route of delivery. With the systemic intravenous delivery, only a small fraction of NPs has the possibility of reaching the target site, even in case of targeted NPs. Thus, a large number of NPs could remain in systemic circulation, leading to drug accumulation or systemic toxicity, and affecting the health of patients [37; 185]. For this reason, other delivery routes, such as localized delivery via intratumoral injection have been studied. Localized delivery can be advantageous particularly in tumor sites where conventional systemic delivery routes fail, enabling the accumulation of the delivered NP at higher concentrations in the targeted tumor volume. Consequently, the use NPs localized delivery strategies helps to avoid repeated dosing, to decrease the final toxicity, and to increase patient compliance [186]. To improve the beneficial effect of localized delivery strategies, recently NP-loaded or drug-embedded implants have been obtained from biodegradable polymers. NP can degrade into biocompatible compounds that are easily absorbed in the body with virtually no side effects [187; 188]. The final evaluation of the anticancer performances of each type of nanoparticles relies on many factors. The radiotherapeutic performance of nanoparticles is affected by their intrinsic parameters, mainly size, shape, surface charge/functionalization, and toxicity, as well as by external factors, such as the targeted type of tumor, the administration methodology, and the irradiation setup [76; 189; 190]. From this picture coupled to the description of the issue on the energy/dose deposition in heavy or hybrid materials at the nanoscale (Sections 3 and 4), it is clear that the comprehension of the physical phenomena occurring in NP exploited in X-rays-based oncotherapy, together with deeper studies for the engineering of nanoparticles performances and targeting, are mandatory. The research for a guideline towards the assessment of the relationship between the NPs key physico-chemical parameters and their therapeutic efficacy in RT is an open roundtable. However, it represents a challenging matter for the chance to design NPs with properties and performances that can be appropriate to address all the pending requests made by the clinical advanced therapies, to increase the survivor rate in oncology, and to improve the life quality of oncological patients.