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For a while, gold nanoparticles (AuNPs) have been recognized as potential radiosensitizers in cancer radiation therapy, mainly due to their physical properties, making them appealing for medical applications. Nevertheless, the performance of AuNPs as radiosensitizers still raises important questions that need further investigation. Searching for selective prostate (PCa) radiosensitizing agents, we studied the radiosensitization capability of the target-specific AuNP-BBN in cancer versus non-cancerous prostate cells, including the evaluation of dose rate effects in comparison with non-targeted counterparts (AuNP-TDOTA). PCa cells were found to exhibit increased AuNP uptake when compared to non-tumoral ones, leading to a significant loss of cellular proliferation ability and complex DNA damage, evidenced by the occurrence of multiple micronucleus per binucleated cell, in the case of PC3 cells irradiated with 2 Gy of γ-rays, after incubation with AuNP-BBN. Remarkably, the treatment of the PC3 cells with AuNP-BBN led to a much stronger influence of the dose rate on the cellular survival upon γ-photon irradiation, as well as on their genomic instability. Overall, AuNP-BBN emerged in this study as a very promising nanotool for the efficient and selective radiosensitization of human prostate cancer PC3 cells, therefore deserving further preclinical evaluation in adequate animal models for prostate cancer radiotherapy.

Ionizing radiation is a common and effective therapeutic option for the treatment of glioblastoma (GBM). Unfortunately, some GBMs are relatively radioresistant and patients have worse outcomes after radiation treatment. The mechanisms underlying intrinsic radioresistance in GBM has been rigorously investigated over the past several years, but the complex interaction of the cellular molecules and signaling pathways involved in radioresistance remains incompletely defined. A clinically effective radiosensitizer that overcomes radioresistance has yet to be identified. In this review, we discuss the current status of radiation treatment in GBM, including advances in imaging techniques that have facilitated more accurate diagnosis, and the identified mechanisms of GBM radioresistance. In addition, we provide a summary of the candidate GBM radiosensitizers being investigated, including an update of subjects enrolled in clinical trials. Overall, this review highlights the importance of understanding the mechanisms of GBM radioresistance to facilitate the development of effective radiosensitizers.

Nanoparticles have unique, size-dependent properties, which means they are widely used in various branches of industry. The ability to control the properties of nanoparticles makes these nanomaterials very interesting for medicine and pharmacology. The application of nanoparticles in medicine is associated with the design of specific nanostructures, which can be used as novel diagnostic and therapeutic modalities. There are a lot of applications of nanoparticles, e.g., as drug delivery systems, radiosensitizers in radiation or proton therapy, in bioimaging, or as bactericides/fungicides. This paper aims to introduce the characteristics of noble metal-based nanoparticles with particular emphasis on their applications in medicine and related sciences.

Background Radiotherapy is a commonly used tool in clinical practice to treat solid tumors. However, due to the unique microenvironment inside the tumor, such as high levels of GSH, overexpressed H 2 O 2 and hypoxia, these factors can seriously affect the effectiveness of radiotherapy. Results Therefore, to further improve the efficiency of radiotherapy, a core–shell nanocomposite CeO 2 –MnO 2 is designed as a novel radiosensitizer that can modulate the tumor microenvironment (TME) and thus improve the efficacy of radiation therapy. CeO 2 –MnO 2 can act as a radiosensitizer to enhance X-ray absorption at the tumor site while triggering the response behavior associated with the tumor microenvironment. According to in vivo and in vitro experiments, the nanoparticles aggravate the killing effect on tumor cells by generating large amounts of ROS and disrupting the redox balance. In this process, the outer layer of MnO 2 reacts with GSH and H 2 O 2 in the tumor microenvironment to generate ROS and release oxygen, thus alleviating the hypoxic condition in the tumor area. Meanwhile, the manganese ions produced by degradation can enhance T1-weighted magnetic resonance imaging (MRI). In addition, CeO 2 –MnO 2 , due to its high atomic number oxide CeO 2 , releases a large number of electrons under the effect of radiotherapy, which further reacts with intracellular molecules to produce reactive oxygen species and enhances the killing effect on tumor cells, thus having the effect of radiotherapy sensitization. In conclusion, the nanomaterial CeO 2 –MnO 2 , as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystem with radiosensitizing function. Conclusion In conclusion, the nanomaterial CeO 2 –MnO 2 , as a novel radiosensitizer, greatly improves the efficiency of cancer radiation therapy by improving the lack of oxygen in tumor and responding to the tumor microenvironment, providing an effective strategy for the construction of nanosystems with radiosensitizing function.

Local hypoxia in solid tumors often results in resistance to radiotherapy （RT）, in which oxygen is an essential element for enhancing DNA damage caused by ionizing radiation. Herein, we developed gold@manganese dioxide （Au@MnO2） core-shell nanoparticles with a polyethylene glycol （PEG） coating as a novel radiosensitizing agent to improve RT efficacy during cancer treatment. In this Au@MnO2 nanostructure, while the gold core is a well-known RT sensitizer that interacts with X-rays to produce charged particles for improved cancer killing under RT, the MnO2 shell may trigger the decomposition of endogenous H2O2 in the tumor microenvironment to generate oxygen and overcome hypoxiaassociated RT resistance. As demonstrated by both in vitro and in vivo experiments, Au@MnO2-PEG nanoparticles acted as effective radiosensitizers to remarkably enhance cancer treatment efficacy during RT. Moreover, no obvious side effects of Au@MnO2-PEG were observed in mice. Therefore, our work presents a new type of radiosensitizer with potential for enhanced RT treatment of hypoxic tumors.

BackgroundGlioblastoma is the most common malignant brain tumor in human adults. Despite several improvements in resective as well as adjuvant therapy over the last decades, its overall prognosis remains poor. As a means of improving patient outcome, the possibility of enhancing radiation response by using radiosensitizing agents has been tested in an array of studies.MethodsA comprehensive review of clinical trials involving radiation therapy in combination with radiosensitizing agents on patients diagnosed with glioblastoma was performed in the National Center for Biotechnology Information’s PubMed database.ResultsA total of 96 papers addressing this matter were published between 1976 and 2021, of which 63 matched the subject of this paper. All papers were reviewed, and their findings discussed in the context of their underlining mechanisms of radiosensitization.ConclusionIn the history of glioblastoma treatment, several approaches of optimizing radiation-effectiveness using radiosensitizers have been made. Even though several different strategies and agents have been explored, clear evidence of improved patient outcome is still missing. Tissue-selectiveness and penetration of the blood–brain barrier seem to be major roadblocks; nevertheless, modern strategies try to circumvent these obstacles, using novel sensitizers based on preclinical data or alternative ways of delivery.

Conventional cancer treatment is mainly based on the surgical removal of the tumor followed by radiotherapy and/or chemotherapy. When surgical removal is not possible, radiotherapy and, less often, chemotherapy is the only way to treat patients. However, despite significant progress in understanding the molecular mechanisms of carcinogenesis and developments in modern radiotherapy techniques, radiotherapy (alone or in combination) does not always guarantee treatment success. One of the main causes is the radioresistance of cancer cells. Increasing the radiosensitivity of cancer cells improves the processes leading to their elimination during radiotherapy and prolonging the survival of cancer patients. In order to enhance the effect of radiotherapy in the treatment of radioresistant neoplasms, radiosensitizers are used. In clinical practice, synthetic radiosensitizers are commonly applied, but scientists have recently focused on using natural products (phytocompounds) as adjuvants in radiotherapy. In this review article, we only discuss naturally occurring radiosensitizers currently in clinical trials (paclitaxel, curcumin, genistein, and papaverine) and those whose radiation sensitizing effects, such as resveratrol, have been repeatedly confirmed by many independent studies.

Sanazole is a hypoxic radiosensitizer for which the activation mechanism in cells has been suggested to involve initial reduction. Herein, electron attachment to sanazole under isolated conditions and upon microhydrations is investigated. Employing mass spectrometry supported by quantum chemical calculations, the anion formation mechanism and subsequent fragmentation pathways are examined. In the case of electron attachment to the isolated molecule, predominantly dissociative electron attachment is observed. The most prominent fragment anion, (NTR‐yl)− at m/z 113, is suggested to be formed in an exothermic pathway through a single‐bond dissociation, whereas other intense fragments require structural reorganization. The limited abundance of the parent anion under isolated conditions is altered upon microhydration conditions since in the latter situation only the (microhydrated) parent anion is observed. This result suggests that hydration closes and/or slows down the dissociation process and indicates that for sanazole, the initial mechanism of action in a reductive cell environment may be similar to that of well‐studied nitroimidazole radiosensitizers. Employing mass spectrometry supported by quantum chemical calculations, electron attachment to gas‐phase and microhydrated sanazole, a hypoxic radiosensitizer, is examined. The results suggest that hydration closes and/or slows down the dissociation process and indicates that the initial mechanism of action in a reductive cell environment may be similar to that of well‐studied nitroimidazole radiosensitizers.

Over the last decade, a growing interest in the improvement of radiation therapies has led to the development of gold-based nanomaterials as radiosensitizer. Although the radiosensitization effect was initially attributed to a dose enhancement mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of chemical and biological contributions. Despite extensive experimental validation, the debate regarding the mechanism(s) of gold nanoparticle radiosensitization is limiting its clinical translation. This article reviews the current state of knowledge by addressing how gold nanoparticles exert their radiosensitizing effects from a transdisciplinary perspective. We also discuss the current and future challenges to go towards a successful clinical translation of this promising therapeutic approach.

Radiation therapy effectively treats prostate cancer, but tumor recurrence remains a clinical challenge, highlighting the need for strategies to enhance radiosensitivity. In this study, we developed a simple, high‐throughput drug repurposing screening platform to find radiosensitizers from compounds approved by the U.S. Food and Drug Administration. A library of 1134 compounds was systematically screened at two concentrations (0.2 and 2 μM) using LNCaP cells stably expressing Metridia luciferase, allowing highly sensitive and quantitative assessment of cell viability through luciferase activity in culture supernatants. In the primary screening, 8 and 12 candidate radiosensitizers were identified at 0.2 μM and 2 μM, respectively. In the secondary screening, 19 compounds were evaluated at two radiation doses (4 Gy and 6 Gy) and six drug concentrations, identifying 5 radiation‐sensitizing candidate compounds. Through this stepwise screening approach, cladribine was identified as the most potent radiosensitizer. Cladribine increased radiation‐induced cytotoxicity in multiple prostate cancer cell lines (22Rv1, DU145, and PC3), with dose‐modifying factors of 1.46, 1.55, and 1.43, respectively, based on the radiation dose needed to achieve 90% cell death. Mechanistically, cladribine prevented the repair of radiation‐induced DNA double‐strand breaks, shown by increased γH2AX levels. Importantly, its radiosensitizing effect was further confirmed in vivo using 22Rv1 and DU145 xenograft models. This study demonstrates that a luciferase‐based high‐throughput drug repurposing platform is useful for identifying clinically relevant radiosensitizers, revealing that cladribine is a promising candidate for further translational research in prostate cancer radiotherapy. The combination of cladribine and irradiation significantly suppressed the growth of DU145‐derived tumors compared with the DMSO plus irradiation group in the mouse model. In addition, it also elevated the percentage of γH2AX‐positive cells after irradiation.