Fragmentation of 5-fluorouridine induced by low energy (< 12 eV) electrons: insights into the radiosensitization of DNA.

5-Fluorouracil is now routinely used in chemo- and radiotherapy. Incorporated within DNA, the molecule is bound to the sugar backbone, forming the 5-fluorouridine sub-unit investigated in the present work. For the clinical usage of the latter, no information exists on the mechanisms that control the radiosensitizing effect at the molecular level. As low energy (< 12 eV) electrons are abundantly produced along the radiation tracks during cancer treatment using beams of high energy particles, we study how these ballistic secondary electrons damage the sensitizing molecule. The salient result from our study shows that the N-glycosidic bonds are principally affected with a cross-section of approximately two orders of magnitude higher than the canonical thymidine, reflecting to some degree the surviving factor of radiation-treated carcinoma cells with and without 5-fluorouracil incorporation. This result may help in the comprehension of the radiosensitizing effect of the fluoro-substituted thymidine in DNA.

A simulation study on the radiosensitization properties of gold nanorods.

Objective. Gold nanorods (GNRs) have emerged as versatile nanoparticles with unique properties, holding promise in various modalities of cancer treatment through drug delivery and photothermal therapy. In the rapidly evolving field of nanoparticle radiosensitization (NPRS) for cancer therapy, this study assessed the potential of gold nanorods as radiosensitizing agents by quantifying the key features of NPRS, such as secondary electron emission and dose enhancement, using Monte Carlo simulations.Approach. Employing the TOPAS track structure code, we conducted a comprehensive evaluation of the radiosensitization behavior of spherical gold nanoparticles and gold nanorods. We systematically explored the impact of nanorod geometry (in particular size and aspect ratio) and orientation on secondary electron emission and deposited energy ratio, providing validated results against previously published simulations.Main results. Our findings demonstrate that gold nanorods exhibit comparable secondary electron emission to their spherical counterparts. Notably, nanorods with smaller surface-area-to-volume ratios (SA:V) and alignment with the incident photon beam proved to be more efficient radiosensitizing agents, showing superiority in emitted electron fluence. However, in the microscale, the deposited energy ratio (DER) was not markedly influenced by the SA:V of the nanorod. Additionally, our findings revealed that the geometry of gold nanoparticles has a more significant impact on the emission of M-shell Auger electrons (with energies below 3.5 keV) than on higher-energy electrons.Significance. This research investigated the radiosensitization properties of gold nanorods, positioning them as promising alternatives to the more conventionally studied spherical gold nanoparticles in the context of cancer research. With increasing interest in multimodal cancer therapy, our findings have the potential to contribute valuable insights into the perspective of gold nanorods as effective multipurpose agents for synergistic photothermal therapy and radiotherapy. Future directions may involve exploring alternative metallic nanorods as well as further optimizing the geometry and coating materials, opening new possibilities for more effective cancer treatments.

Radiosensitizing Effect of Dextran-Coated Iron Oxide Nanoparticles on Malignant Glioma Cells.

The potential of standard methods of radiation therapy is limited by the dose that can be safely delivered to the tumor, which could be too low for radical treatment. The dose efficiency can be increased by using radiosensitizers. In this study, we evaluated the sensitizing potential of biocompatible iron oxide nanoparticles coated with a dextran shell in A172 and Gl-Tr glioblastoma cells in vitro. The cells preincubated with nanoparticles for 24 h were exposed to ionizing radiation (X-ray, gamma, or proton) at doses of 0.5-6 Gy, and their viability was assessed by the Resazurin assay and by staining of the surviving cells with crystal violet. A statistically significant effect of radiosensitization by nanoparticles was observed in both cell lines when cells were exposed to 35 keV X-rays. A weak radiosensitizing effect was found only in the Gl-Tr line for the 1.2 MeV gamma irradiation and there was no radiosensitizing effect in both lines for the 200 MeV proton irradiation at the Bragg peak. A slight (ca. 10%) increase in the formation of additional reactive oxygen species after X-ray irradiation was found when nanoparticles were present. These results suggest that the nanoparticles absorbed by glioma cells can produce a significant radiosensitizing effect, probably due to the action of secondary electrons generated by the magnetite core, whereas the dextran shell of the nanoparticles used in these experiments appears to be rather stable under radiation exposure.

Dissociative Electron Attachment to 5-Iodo-4-thio-2'-deoxyuridine: A Potential Radiosensitizer of Hypoxic Cells.

In the search for effective radiosensitizers for tumor cells, halogenated uracils have attracted more attention due to their large cross section for dissociation upon the attachment of low-energy electrons. In this study, we investigated dissociative electron attachment (DEA) to 5-iodo-4-thio-2'-deoxyuridine, a potential radiosensitizer using a crossed electron-molecule beam experiment coupled with quadrupole mass spectrometry. The experimental results were supported by calculations on the threshold energies of formed anions and transition state calculations. We show that low-energy electrons with kinetic energies near 0 eV may effectively decompose the molecule upon DEA. The by far most abundant anion observed corresponds to the iodine anion (I-). Due to the associated bond cleavage, a radical site is formed at the C5 position, which may initiate strand break formation if the molecule is incorporated into a DNA strand. Our results reflect the conclusion from previous radiolysis studies with the title compound, suggesting its potential as a radiosensitizer.

A review of bismuth-based nanoparticles and their applications in radiosensitising and dose enhancement for cancer radiation therapy.

About 50% of cancer patients receive radiation therapy. Despite the therapeutic benefits of this method, the toxicity of radiation in the normal tissues is unavoidable To improve the quality of radiation therapy, in addition to other methods such as IMRT, IGRT, and high radiation dose, nanoparticles have shown excellent potential when ionising radiation is applied to the target volume. Recently, bismuth-based nanoparticles (BiNPs) have become particularly popular in radiation therapy due to their high atomic numbers (Z), high X-ray attenuation coefficient, low toxicity, and low cost. Moreover, it is easy to synthesise in a variety of sizes and shapes. This study aimed to review the effects of the bismuth-based NP and its combination with other compounds, and their potential synergies in radiotherapy, discussed based on their physical, chemical, and biological interactions. Targeted and non-targeted bismuth-based NPs used in radiotherapy as radiosensitizers and dose enhancement effects are described. The results reported in the literature were categorised into various groups. Also, this review has highlighted the importance of bismuth-based NPs in different forms of cancer treatment to find the highest efficiency for applying them as a suitable candidate for various cancer therapy and future clinical applications.

Critical parameters to translate gold nanoparticles as radiosensitizing agents into the clinic.

Radiotherapy is an inevitable choice for cancer treatment that is applied as combinatorial therapy along with surgery and chemotherapy. Nevertheless, radiotherapy at high doses kills normal and tumor cells at the same time. In addition, some tumor cells are resistant to radiotherapy. Recently, many researchers have focused on high-Z nanomaterials as radiosensitizers for radiotherapy. Among them, gold nanoparticles (GNPs) have shown remarkable potential due to their promising physical, chemical, and biological properties. Although few clinical trial studies have been performed on drug delivery and photosensitization with lasers, GNPs have not yet received Food and Drug Administration approval for use in radiotherapy. The sensitization effects of GNPs are dependent on their concentration in cells and x-ray energy deposition during radiotherapy. Notably, some limitations related to the properties of the GNPs, including their size, shape, surface charge, and ligands, and the radiation source energy should be resolved. At the first, this review focuses on some of the challenges of using GNPs as radiosensitizers and some biases among in vitro/in vivo, Monte Carlo, and clinical studies. Then, we discuss the challenges in the clinical translation of GNPs as radiosensitizers for radiotherapy and proposes feasible solutions. And finally, we suggest that certain areas be considered in future research. This article is categorized under: Therapeutic Approaches and Drug Discovery > NA.

Mechanisms of Nanoscale Radiation Enhancement by Metal Nanoparticles: Role of Low Energy Electrons.

Metal nanoparticles are considered as highly promising radiosensitizers in cancer radiotherapy. Understanding their radiosensitization mechanisms is critical for future clinical applications. This review is focused on the initial energy deposition by short-range Auger electrons; when high energy radiation is absorbed by gold nanoparticles (GNPs) located near vital biomolecules; such as DNA. Auger electrons and the subsequent production of secondary low energy electrons (LEEs) are responsible for most the ensuing chemical damage near such molecules. We highlight recent progress on DNA damage induced by the LEEs produced abundantly within about 100 nanometers from irradiated GNPs; and by those emitted by high energy electrons and X-rays incident on metal surfaces under differing atmospheric environments. LEEs strongly react within cells; mainly via bound breaking processes due to transient anion formation and dissociative electron attachment. The enhancement of damages induced in plasmid DNA by LEEs; with or without the binding of chemotherapeutic drugs; are explained by the fundamental mechanisms of LEE interactions with simple molecules and specific sites on nucleotides. We address the major challenge of metal nanoparticle and GNP radiosensitization; i.e., to deliver the maximum local dose of radiation to the most sensitive target of cancer cells (i.e., DNA). To achieve this goal the emitted electrons from the absorbed high energy radiation must be short range, and produce a large local density of LEEs, and the initial radiation must have the highest possible absorption coefficient compared to that of soft tissue (e.g., 20-80 keV X-rays).

Novel strategies for tumor radiosensitization mediated by multifunctional gold-based nanomaterials.

Radiotherapy (RT) is one of the most effective and commonly used cancer treatments for malignant tumors. However, the existing radiosensitizers have a lot of side effects and poor efficacy, which limits the curative effect and further application of radiotherapy. In recent years, emerging nanomaterials have shown unique advantages in enhancing radiosensitization. In particular, gold-based nanomaterials, with high X-ray attenuation capacity, good biocompatibility, and promising chemical, electronic and optical properties, have become a new type of radiotherapy sensitizer. In addition, gold-based nanomaterials can be used as a carrier to load a variety of drugs and immunosuppressants; in particular, its photothermal therapy, photodynamic therapy and multi-mode imaging functions aid in providing excellent therapeutic effect in coordination with RT. Recently, many novel strategies of radiosensitization mediated by multifunctional gold-based nanomaterials have been reported, which provides a new idea for improving the efficacy and reducing the side effects of RT. In this review, we systematically summarize the recent progress of various new gold-based nanomaterials that mediate radiosensitization and describe the mechanism. We further discuss the challenges and prospects in the field. It is hoped that this review will help researchers understand the latest progress of gold-based nanomaterials for radiosensitization, and encourage people to optimize the existing methods or explore novel approaches for radiotherapy.

One Stone, Two Birds: A Peptide-Au(I) Infinite Coordination Supermolecule for the Confederate Physical and Biological Radiosensitization in Cancer Radiation Therapy.

Over half of cancer patients are subjected to radiotherapy, but owing to the deficient amount of reactive oxygen radicals (ROS) and DNA double-strand breaks (DSBs), a fair number of them suffer from radiotherapy resistance and the subsequent short-term survival opportunity. To overcome it, many successes have been achieved in radiosensitizer discovery using physical strategy and/or biological strategy, but significant challenges remain regarding developing clinically translational radiosensitizers. Herein, a peptide-Au(I) infinite coordination supermolecule termed PAICS is developed that combined both physical and biological radiosensitization and possessed pharmaceutical characteristics including adequate circulatory stability, controllable drug release, tumor-prioritized accumulation, and the favorable body eliminability. As expected, monovalent gold ion endowed this supermolecule with high X-ray absorption and the subsequent radiosensitization. Furthermore, a peptide targeting CRM1, is assembled into the supermolecule, which successfully activates p53 and apoptosis pathway, thereby further sensitizing radiotherapy. As a result, PAICS showed superior ability for radiotherapy sensitization in vivo and maintained a favorable safety profile. Thus, the PAICS reported here will offer a feasible solution to simultaneously overcome both the pharmaceutical obstacles of physical and biological radiosensitizers and will enable the development of a class of nanomedicines for tumor radiotherapy sensitization.

Electron attachment to fluorodeoxyglucose: Dissociation dynamics in a molecule of near-zero electron affinity.

Fluorodeoxyglucose (FDG) is a glucose derivative with fluorine at the C2 position. The molecule containing the radioactive F-18 isotope is well known from its application in positron emission tomography as a radiotracer in tumor examination. In the stable form with the F-19 isotope, FDG was proposed as a potential radiosensitizer. Since reduction processes may be relevant in radiosensitization, we investigated low-energy electron attachment to FDG with a crossed electron-molecule beam experiment and with quantum chemical calculations as well as molecular dynamics at elevated temperatures to reveal statistical dissociation. We experimentally find that the susceptibility of FDG to low-energy electrons is relatively low. The calculations indicate that upon attachment of an electron with a kinetic energy of ∼0 eV, only dipole-bound states are accessible, which agrees with the weak ion yields observed in the experiment. The temporary negative ions formed upon electron attachment to FDG may decay by a large variety of dissociation reactions. The major fragmentation channels include H2O, HF, and H2 dissociation, accompanied by ring opening.

HF Formation through Dissociative Electron Attachment-A Combined Experimental and Theoretical Study on Pentafluorothiophenol and 2-Fluorothiophenol.

In chemoradiation therapy, dissociative electron attachment (DEA) may play an important role with respect to the efficiency of the radiosensitizers used. The rational tailoring of such radiosensitizers to be more susceptive to DEA may thus offer a path to increase their efficiency. Potentially, this may be achieved by tailoring rearrangement reactions into the DEA process such that these may proceed at low incident electron energies, where DEA is most effective. Favorably altering the orbital structure of the respective molecules through substitution is another path that may be taken to promote dissociation up on electron capture. Here we present a combined experimental and theoretical study on DEA in relation to pentafluorothiophenol (PFTP) and 2-fluorothiophenol (2-FTP). We investigate the thermochemistry and dynamics of neutral HF formation through DEA as means to lower the threshold for dissociation up on electron capture to these compounds, and we explore the influence of perfluorination on their orbital structure. Fragment ion yield curves are presented, and the thermochemical thresholds for the respective DEA processes are computed as well as the minimum energy paths for HF formation up on electron capture and the underlying orbital structure of the respective molecular anions. We show that perfluorination of the aromatic ring in these compounds plays an important role in enabling HF formation by further lowering the threshold for this process and through favorable influence on the orbital structure, such that DEA is promoted. We argue that this approach may offer a path for tailoring new and efficient radiosensitizers.

Near-Infrared Light-Excited Reactive Oxygen Species Generation by Thulium Oxide Nanoparticles.

Exploring materials that can absorb near-infrared (NIR) light to produce reactive oxygen species (ROS) is necessary for many fields. Herein we show that thulium oxide nanoparticles are viable for NIR-stimulated ROS generation. This property may be related to the unique energy levels, large absorption cross section, low fluorescence emission, and ∼10-3 s lifetime of the 3H4 state of Tm ions. We further demonstrate the impact of these nanoparticles on photodynamic therapy (PDT), in which impressive tumor inhibition was recorded after exposure to either a broadband halogen lamp or an 808 nm laser. Our results may provide insight into the areas of photocatalysis, pollution treatment, and fine chemical synthesis.

Cytotoxic Activity of a Unique Monomeric Heterogeneous Two-Coordinate Ligand Monovalent Gold Complex with Tiopronin and a Heterocyclic Mercapto-Tetrazole Compound.

BACKGROUND: The importance of the role of NF-κB is recognized in situations such as malignant transformation and metastasis of cancer, and it has been suggested that inhibiting this role can be one of the cancer treatment strategies. Gold preparations such as auranofin are known to have an indirect NF-κB inhibitory effect. OBJECTIVE: We synthesized a novel gold complex [tiopronin monovalent gold-5-mercapto- 1-methyl tetrazole, abbreviated as TPN-Au(I)-MM4], with different physical properties and chemical structure from auranofin, and evaluated its cytotoxic activity and radiation sensitizing effect on human THP1 cells. METHODS: The number of viable cells was counted by the trypan blue dye exclusion method. The cell death evaluation was performed by FITC-Annexin V+ and PI staining. In investigating the radiation sensitizing effect of TPN-Au(I)-MM4, this compound [10 or 25 µM] was added into the culture medium 1 h before X-ray irradiation. RESULTS: In the cells treated with 25 µM TPN-Au(I)-MM4 for 72 h, a decrease in the proliferation of THP1 cells was observed [The relative values of viable cells in the control group and the 25 µM treatment group were approximately 6.8 and 4.2, respectively]. In the combination of 25 µM of the compound treatment and X-ray irradiation, an increase of approximately 3.0-fold was observed in 2 Gy irradiation and approximately 1.4-fold in 4 Gy irradiation as in comparison to the case of irradiation alone. CONCLUSION: These results suggest that TPN-Au(I)-MM4 reduces the proliferation of THP1 cells through the induction of cell death, and the combined use of TPN-Au(I)-MM4 and X-ray irradiation shows effective cytotoxicity against THP1 cells.

A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model.

BACKGROUND: Combining radiotherapy with PD1 blockade has had impressive antitumor effects in preclinical models of metastatic lung cancer, although anti-PD1 resistance remains problematic. Here, we report results from a triple-combination therapy in which NBTXR3, a clinically approved nanoparticle radioenhancer, is combined with high-dose radiation (HDXRT) to a primary tumor plus low-dose radiation (LDXRT) to a secondary tumor along with checkpoint blockade in a mouse model of anti-PD1-resistant metastatic lung cancer. METHODS: Mice were inoculated with 344SQR cells in the right legs on day 0 (primary tumor) and the left legs on day 3 (secondary tumor). Immune checkpoint inhibitors (ICIs), including anti-PD1 (200 µg) and anti-CTLA4 (100 µg) were given intraperitoneally. Primary tumors were injected with NBTXR3 on day 6 and irradiated with 12-Gy (HDXRT) on days 7, 8, and 9; secondary tumors were irradiated with 1-Gy (LDXRT) on days 12 and 13. The survivor mice at day 178 were rechallenged with 344SQR cells and tumor growth monitored thereafter. RESULTS: NBTXR3 + HDXRT + LDXRT + ICIs had significant antitumor effects against both primary and secondary tumors, improving the survival rate from 0 to 50%. Immune profiling of the secondary tumors revealed that NBTXR3 + HDXRT + LDXRT increased CD8 T-cell infiltration and decreased the number of regulatory T (Treg) cells. Finally, none of the re-challenged mice developed tumors, and they had higher percentages of CD4 memory T cells and CD4 and CD8 T cells in both blood and spleen relative to untreated mice. CONCLUSIONS: NBTXR3 nanoparticle in combination with radioimmunotherapy significantly improves anti-PD1 resistant lung tumor control via promoting antitumor immune response.

A multifunctional AIE gold cluster-based theranostic system: tumor-targeted imaging and Fenton reaction-assisted enhanced radiotherapy.

BACKGROUND: As cancer is one of the main leading causes of mortality, a series of monotherapies such as chemotherapy, gene therapy and radiotherapy have been developed to overcome this thorny problem. However, a single treatment approach could not achieve satisfactory effect in many experimental explorations. RESULTS: In this study, we report the fabrication of cyclic RGD peptide (cRGD) modified Au4-iron oxide nanoparticle (Au4-IO NP-cRGD) based on aggregation-induced emission (AIE) as a multifunctional theranostic system. Besides Au4 cluster-based fluorescence imaging and enhanced radiotherapy, iron oxide (IO) nanocluster could realize magnetic resonance (MR) imaging and Fenton reaction-based chemotherapy. Abundant toxic reactive oxygen species generated from X-ray irradiation and in situ tumor-specific Fenton reaction under acidic microenvironment leads to the apoptotic and necrotic death of cancer cells. In vivo studies demonstrated good biocompatibility of Au4-IO NP-cRGD and a high tumor suppression rate of 81.1% in the synergistic therapy group. CONCLUSIONS: The successful dual-modal imaging and combined tumor therapy demonstrated AIE as a promising strategy for constructing multifunctional cancer theranostic platform.

Harnessing the Power of Kiwifruit for Radiosensitization of Melanoma.

BACKGROUND: Melanoma is the deadliest variant of skin cancer and its incidence continues to increase. There are limited treatment options for advanced and metastatic cases of melanoma, despite advances in immunotherapy and chemotherapy. Melanoma is notorious as a radioresistant tumor. Previous studies found that phytochemicals, such as resveratrol and those found in green tea and blueberry, can sensitize various cancer cells, including melanoma, to radiotherapy. Our previous study also revealed that kiwifruit extract (KE) has antitumor activity to melanoma cells. This study was designed to expand upon our previous investigation and determine KE's potential as a radiosensitizer on CRL-11147 melanoma cancer cells and elucidate the possible mechanisms behind its potential. MATERIALS AND METHODS: Proliferation and apoptosis of CRL-11147 melanoma cells under radiation therapy (RT) plus KE versus RT alone were investigated using Proliferative cell nuclear antigen (PCNA) staining, quick cell proliferation assay, clonogenic assay, and caspase-3 activity assay. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were then used to investigate the mechanisms behind the observed results. RESULTS: The percentage of CRL-11147 colonies, PCNA staining intensity, and the optic density value of CRL-11147 cells decreased with RT/KE vs. RT alone. Relative caspase-3 activity was increased with RT/KE vs. RT alone. Increased expression of the anti-proliferative molecule p27 and pro-apoptotic molecule TRAILR1 correlated with the anti-tumor effect seen in the RT/KE group versus the RT alone group. CONCLUSION: KE augments radiosensitivity of CRL-11147 by up-regulating both p27 and TRAILR1 to inhibit proliferation and increase apoptosis, respectively.

Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy.

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Stimulus-responsive nanomaterials under physical regulation for biomedical applications.

Cancer is a growing threat to human beings. Traditional treatments for malignant tumors usually involve invasive means to healthy human tissues, such as surgical treatment and chemotherapy. In recent years the use of specific stimulus-responsive materials in combination with some non-contact, non-invasive stimuli can lead to better efficacy and has become an important area of research. It promises to develop personalized treatment systems for four types of physical stimuli: light, ultrasound, magnetic field, and temperature. Nanomaterials that are responsive to these stimuli can be used to enhance drug delivery, cancer treatment, and tissue engineering. This paper reviews the principles of the stimuli mentioned above, their effects on materials, and how they work with nanomaterials. For this aim, we focus on specific applications in controlled drug release, cancer therapy, tissue engineering, and virus detection, with particular reference to recent photothermal, photodynamic, sonodynamic, magnetothermal, radiation, and other types of therapies. It is instructive for the future development of stimulus-responsive nanomaterials for these aspects.

Synthesis of 3-octadecanoxypropyl 6-deoxy-6-sulfo-α-d-glucopyranoside (ODSG) as a lipase-resistant SQAP derivative.

Sulfoquynovosylacyl propanediol (SQAP; 1) has been developed as a radiosensitizer (anti-cancer agent) for solid tumors, but it was easily cleaved in vivo and had a problem of short residence time. We synthesized a novel compound of a SQAP derivative (3-octadecanoxypropyl 6-deoxy-6-sulfo-α-d-glucopyranoside: ODSG; 2) to solve these problems not easily cleaved by lipase. ODSG (2) cytotoxicity was investigated in vitro, resulting in low toxicity like SQAP (1).

Breast cancer suppression by curcumin-naringenin-magnetic-nano-particles: In vitro and in vivo studies.

BACKGROUND: The limitations of surgery, radiotherapy, and chemotherapy in cancer treatment and the increase in the application of nanomaterials in the field of biomedicine have promoted the use of nanomaterials in combination with radiotherapy for cancer treatment. OBJECTIVE: To improve the efficiency of cancer treatment, curcumin-naringenin loaded dextran-coated magnetic nanoparticles (CUR-NAR-D-MNPs) were used as chemotherapy and in combination with radiotherapy to verify their effectiveness in treating tumors. METHODS: CUR-NAR-D-MNPs were prepared and studied by several characterization methods. Median inhibitory concentration (IC50) and cellular toxicity were evaluated by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. The cell death and radiosensitization were studied by acridine orange/ethidium bromide dual staining of MCF-7 human breast cancer cells. RESULTS: CUR-NAR-D-MNPs induce apoptosis and inhibited cell proliferation through reactive oxygen species (ROS) generation. CUR-NAR-D-MNPs used alone had a certain therapeutic effect on tumors. CUR-NAR-D-MNPs plus radiotherapy significantly reduced the tumor volume and led to cell cycle arrest and induction of apoptosis through modulation of P53high, P21high, TNF-αlow, CD44low, and ROShigh signalingCONCLUSIONS:CUR-NAR-D-MNPs are effective in the treatment of tumors when combined with radiotherapy, and show radiosensitization effects against cancer proliferation in vitro and in vivo.