Radiotherapy-sensitized cancer immunotherapy via cGAS-STING immune pathway by activatable nanocascade reaction.

Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles "turned on" spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.

Increasing the radiation-induced cytotoxicity by silver nanoparticles and docetaxel in prostate cancer cells.

BACKGROUND: Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation. So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells. METHODS: The cytotoxic effects of DTX, SNP and 2 Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24 h after various single and combined treatments. RESULTS: The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells. CONCLUSION: Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.

Ferroptosis: Frenemy of Radiotherapy.

Recently, it was established that ferroptosis, a type of iron-dependent regulated cell death, plays a prominent role in radiotherapy-triggered cell death. Accordingly, ferroptosis inducers attracted a lot of interest as potential radio-synergizing drugs, ultimately enhancing radioresponses and patient outcomes. Nevertheless, the tumor microenvironment seems to have a major impact on ferroptosis induction. The influence of hypoxic conditions is an area of interest, as it remains the principal hurdle in the field of radiotherapy. In this review, we focus on the implications of hypoxic conditions on ferroptosis, contemplating the plausibility of using ferroptosis inducers as clinical radiosensitizers. Furthermore, we dive into the prospects of drug repurposing in the domain of ferroptosis inducers and radiosensitizers. Lastly, the potential adverse effects of ferroptosis inducers on normal tissue were discussed in detail. This review will provide an important framework for subsequent ferroptosis research, ascertaining the feasibility of ferroptosis inducers as clinical radiosensitizers.

Tumor-Targeted Perfluorinated Micelles as Efficient Theranostic Agents Combining Positron Emission Tomography and Radiosensitization.

We report the synthesis of biocompatible perfluorinated micelles designed to improve radiotherapeutic efficacy in a radioresistant tumor environment. In vitro and in vivo behaviors of perfluorinated micelles were assessed at both cellular and tissular levels. The micellar platform offers key advantages as theranostic tool: (i) small size, allowing deep tissue penetration; (ii) oxygen transport to hypoxic tissues; (iii) negligible toxicity in the absence of ionizing radiation; (iv) internalization into cancer cells; (v) potent radiosensitizing effect; and (vi) excellent tumor-targeting properties, as monitored by positron emission tomography. We have demonstrated strong in vitro radiosensitizing effects of the micelle and in vivo tumor targeting, making this nanometric carrier a promising tool for the potentiation of focused radiotherapy.

Janus ACSP Nanoparticle for Synergistic Chemodynamic Therapy and Radiosensitization.

Protective autophagy and DNA damage repair lead to tumor radio-resistance. Some hypoxic tumors exhibit a low radiation energy absorption coefficient in radiation therapy. High doses of X-rays may lead to side effects in the surrounding normal tissues. In order to overcome the radio-resistance and improve the efficacy of radiotherapy based on the characteristics of the tumor microenvironment, the development of radiosensitizers has attracted much attention. In this study, a Janus ACSP nanoparticle (NP) was developed for chemodynamic therapy and radiosensitization. The reactive oxygen species generated by the Fenton-like reaction regulated the distribution of cell cycles from a radioresistant phase to a radio-sensitive phase. The high-Z element, Au, enhanced the production of hydroxyl radicals (•OH) under X-ray radiation, promoting DNA damage and cell apoptosis. The NP delayed DNA damage repair by interfering with certain proteins involved in the DNA repair signaling pathway. In vivo experiments demonstrated that the combination of the copper-ion-based Fenton-like reaction and low-dose X-ray radiation enhanced the effectiveness of radiotherapy, providing a novel approach for synergistic chemodynamic and radiosensitization therapy. This study provides valuable insights and strategies for the development and application of NPs in cancer treatment.

Novel Amidine Derivative K1586 Sensitizes Colorectal Cancer Cells to Ionizing Radiation by Inducing Chk1 Instability.

Checkpoint kinase 1 (Chk1) is a key mediator of the DNA damage response that regulates cell cycle progression, DNA damage repair, and DNA replication. Small-molecule Chk1 inhibitors sensitize cancer cells to genotoxic agents and have shown preclinical activity as single agents in cancers characterized by high levels of replication stress. However, the underlying genetic determinants of Chk1-inhibitor sensitivity remain unclear. Although treatment options for advanced colorectal cancer are limited, radiotherapy is effective. Here, we report that exposure to a novel amidine derivative, K1586, leads to an initial reduction in the proliferative potential of colorectal cancer cells. Cell cycle analysis revealed that the length of the G2/M phase increased with K1586 exposure as a result of Chk1 instability. Exposure to K1586 enhanced the degradation of Chk1 in a time- and dose-dependent manner, increasing replication stress and sensitizing colorectal cancer cells to radiation. Taken together, the results suggest that a novel amidine derivative may have potential as a radiotherapy-sensitization agent that targets Chk1.

Carbon-Iodine Polydiacetylene Nanofibers for Image-Guided Radiotherapy and Tumor-Microenvironment-Enhanced Radiosensitization.

Radiotherapy is a mainstay treatment used in clinics for locoregional therapy, although it still represents a great challenge to improve the sensitivity and accuracy of radiotherapy for tumors. Here, we report the conjugated polymer, polydiiododiacetylene (PIDA), with an iodine content of 84 wt %, as a highly effective computed tomography (CT) contrast agent and tumor microenvironment-responsive radiosensitizer. PIDA exhibited several key properties that contribute to the improvement of precision radiotherapy. The integrated PIDA nanofibers confined within the tumor envelope demonstrated amplified CT intensity and prolonged retention, providing an accurate calculation of dose distribution and precise radiation delivery for CT image-guided radiotherapy. Therefore, our strategy pioneers PIDA nanofibers as a bridge to cleverly connect a fiducial marker to guide accurate radiotherapy and a radiosensitizer to improve tumor sensitivity, thereby minimizing potential damage to surrounding tissues and facilitating on-demand therapeutic intervention in tumors.

Taraxasterol enhanced bladder cancer cells radiosensitivity via inhibiting the COX-2/PGE2/JAK2/STAT3/MMP pathway.

PURPOSE: Radiotherapy with bladder preservation is highly acceptable among patients bearing bladder cancer (BCa), but the occurrence of secondary tolerance (ARR) during treatment is one of the important reasons for the failure of clinical radiotherapy. COX-2 has been frequently reported to be highly expressed and associated with radio-resistance in various cancers. In this study, the feasibility of Taraxasterol (Tara) as a radiosensitizer was investigated, and the target effect of Tara on COX-2 and its underlying mechanism were explored. METHODS AND MATERIALS: The toxicity of Tara toward BCa cells was detected with the MTT method and cells in response to IR or Tara + IR were compared by clone formation assay. Next, a small RNA interference system (siRNA) was employed to decrease endogenous COX-2 expression in BCa cells, and the stem cell-like features and motion abilities of BCa cells under different treatments were investigated using microsphere formation and transwell chamber assay, respectively. Meanwhile, the expression of a series of inflammation-related molecules and stem cell characteristic molecules was determined by qRT-PCR, western blot and ELISA method. In vivo studies, BCa cells were subcutaneously injected into the right flank of each male mouse. Those mice were then grouped and exposed to different treatment: Tara, IR, IR + Tara and untreated control. The volumes of each tumor were measured every two days and target proteins were detected with immunohistochemical (IHC) staining. RESULTS: The results show that COX-2 decline, due to COX-2 knocking-down or Tara treatment, could greatly enhance BCa cells' radiosensitivity and significantly decrease their migration, invasion and microsphere formation abilities, companied with the reduce of JAK2, phos-STAT3, MMP2 and MMP9 expression. However, Tara could not further reduce the expression of an above molecule of cells in COX-2-deficient BCa cells. Correspondingly, Tara treatment could not further enhance those siCOX-2 BCa cells response to IR. CONCLUSIONS: Our data support that Tara can improve the radiosensitivity of BCa cells by targeting COX-2/PGE2. The mechanism may involve regulating STAT3 phosphorylation, DNA damage response protein activation, and expression of MMP2/MMP9.

Radiation therapy for triple-negative breast cancer: from molecular insights to clinical perspectives.

INTRODUCTION: Triple-negative breast cancer (TNBC) lacks three common receptors, making traditional treatments less effective. This review highlights the importance of radiotherapy and emerging therapeutic strategies to enhance treatment outcomes in TNBC. AREAS COVERED: We conducted a literature search on PubMed for publications from 2000 to 2023 to discuss the critical role of radiotherapy in managing TNBC, emphasizing its applications from locoregional control to improving survival rates. The review explores molecular mechanisms underlying TNBC's radiotherapy response, including DNA damage repair and apoptosis, with a focus on BRCA1/2 mutations and Poly (ADP-ribose) polymerase (PARP) inhibition. We summarize preclinical and clinical research on radiosensitization strategies, from gene-targeted therapies to immunotherapy combinations, and the impact of post-mastectomy radiation therapy on locoregional control. The potential of personalized treatment approaches, integrating molecular profiling, targeted radiosensitizers, and the synergistic effects of radiotherapy with immunotherapy, is also discussed. EXPERT OPINION: Future TNBC treatment strategies should focus on precision medicine, integrating immunotherapy, developing novel radiosensitizers, and targeting biological pathways to overcome radioresistance. The integration of radiomics and artificial intelligence offers promising avenues for enhancing treatment personalization and efficacy, aiming to improve patient outcomes in TNBC.

MiR-378a-5p exerts a radiosensitizing effect on CRC through LRP8/ß-catenin axis.

BACKGROUND: MiRNAs are closely related to tumor radiosensitivity. MiR-378a-5p level is down-regulated in colorectal cancer (CRC). Therefore, this study intends to explore the role of miR-378a-5p in CRC, especially radiosensitivity. METHODS: The expression of miR-378a-5p was analyzed in CRC samples. CRC cell lines were treated with different doses of X-rays. Bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were used to detect the expressions and binding relationship of miR-378a-5p and low-density lipoprotein receptor-related protein 8 (LRP8). MiR-378a-5p inhibitor or/and siLRP8 were transfected into CRC cells with or without irradiation. Subsequently, clonogenic assay, flow cytometry and in vivo experiments including tumorigenesis assay, immunohistochemistry, RT-qPCR and Western blot were performed to clarify the role of miR-378a-5p/LRP8 axis in the radiosensitivity of CRC. RESULTS: The down-regulated expression of miR-378a-5p in CRC is related to histological differentiation and tumor-node-metastasis (TNM) stage. After irradiation, the survival fraction of CRC cells was decreased, while the apoptotic rate and the level of miR-378a-5p were increased. Restrained miR-378a-5p repressed apoptosis and apoptosis-related protein expressions, yet promoted the proliferation and the radioresistance of cells by regulating ß-catenin in CRC cells. LRP8 was highly expressed in CRC, and targeted by miR-378a-5p. SiLRP8 improved radiosensitivity and reversed the effect of miR-378a-5p down-regulation on CRC cells. Overexpressed miR-378a-5p and irradiation enhanced the level of miR-378a-5p, yet suppressed the expressions of Ki67 and LRP8 as well as tumorigenesis. CONCLUSION: MiR-378a-5p may exert a radiosensitizing effect on CRC through the LRP8/ß-catenin axis, which may be a new therapeutic target for CRC radioresistance.

Inhibition of the thioredoxin system for radiosensitization therapy of cancer.

Radiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance exhibited by cancer cells, coupled with the adverse effects of RT on normal tissues, often compromises its therapeutic potential and leads to unwanted side effects. This comprehensive review aims to consolidate our understanding of how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including gold nanoparticles (GNPs), gold triethylphosphine cyanide ([Au(SCN) (PEt3)]), auranofin, ceria nanoparticles (CONPs), curcumin and its derivatives, piperlongamide, indolequinone derivatives, micheliolide, motexafin gadolinium, and ethane selenide selenidazole derivatives (SeDs), are meticulously elucidated in terms of their applications in radiotherapy. In this review, the sensitization mechanisms and the current research progress of these radiosensitizers are discussed in detail, with the overall aim of providing valuable insights for the judicious application of Trx system inhibitors in the field of cancer radiosensitization therapy.

Dual-Epigenetically Relieving the MYC-Correlated Immunosuppression via an Advanced Nano-Radiosensitizer Potentiates Cancer Immuno-Radiotherapy.

Cancer cells can upregulate the MYC expression to repair the radiotherapy-triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC-transcriptional abnormality may intensively solve this clinical problem. Herein, 5-Aza (a DNA methyltransferase inhibitor) and ITF-2357 (a histone deacetylase inhibitor) are engineered into a tungsten-based nano-radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5-Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF-2357, which triggers cancer cellular type I interferon (IFN-I) signaling. Coupling 5-Aza with ITF-2357 ensures that PWAI does not evoke the treated model with high MYC-related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN-I signal-related proteins involving IFN-α and IFN-ß. Unlike the radiation treatment alone, PWAI-triggered immuno-radiotherapy remarkably enhances antitumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory-phenotype formation in 4T1 tumor-bearing mice. Downgrading the radiotherapy-induced MYC overexpression via the dual-epigenetic reprogramming strategy may elicit a robust immuno-radiotherapy.

High-definition FT-IR reveals a synergistic effect on lipid accumulation in prostate cancer cells induced by a combination of X-rays and radiosensitizing drugs.

Radiotherapy is one of the most commonly used cancer therapies with many benefits including low toxicity to healthy tissues. However, a major problem in radiotherapy is cancer radioresistance. To enhance the effect of this kind of therapy several approaches have been proposed such as the use of radiosensitizers. A combined treatment of radiotherapy and radiosensitizing drugs leads to a greater effect on cancer cells than anticipated from the addition of both responses (synergism). In this study, high-definition FT-IR imaging was applied to follow lipid accumulation in prostate cancer cells as a response to X-ray irradiation, radiosensitizing drugs, and a combined treatment of X-rays and the drugs. Lipid accumulation induced in the cells by an increasing X-ray dose and the presence of the drugs was analyzed using Principal Component Analysis and lipid staining. Finally, the synergistic effect of the combined therapy (X-rays and radiosensitizers) was confirmed by calculations of the integral intensity of the 2850 cm-1 band.

A bioconvergence study on platinum-free concurrent chemoradiotherapy for the treatment of HPV-negative head and neck carcinoma.

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient's quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts.

Radioresistance of melanoma brain metastases limits the clinical utility of conventionally fractionated brain radiation in this disease, and strategies to improve radiation response could have significant clinical impact. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is critical for repair of radiation-induced DNA damage, and inhibitors of this kinase can have potent effects on radiation sensitivity. In this study, the radiosensitizing effects of the DNA-PKcs inhibitor peposertib were evaluated in patient-derived xenografts of melanoma brain metastases (M12, M15, M27). In clonogenic survival assays, peposertib augmented radiation-induced killing of M12 cells at concentrations ≥100 nmol/L, and a minimum of 16 hours exposure allowed maximal sensitization. This information was integrated with pharmacokinetic modeling to define an optimal dosing regimen for peposertib of 125 mpk dosed just prior to and 7 hours after irradiation. Using this drug dosing regimen in combination with 2.5 Gy × 5 fractions of radiation, significant prolongation in median survival was observed in M12-eGFP (104%; P = 0.0015) and M15 (50%; P = 0.03), while more limited effects were seen in M27 (16%, P = 0.04). These data support the concept of developing peposertib as a radiosensitizer for brain metastases and provide a paradigm for integrating in vitro and pharmacokinetic data to define an optimal radiosensitizing regimen for potent DNA repair inhibitors.

Combining a noble gas with radiotherapy: glutamate receptor antagonist xenon may act as a radiosensitizer in glioblastoma.

BACKGROUND: Ionotropic glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) modulate proliferation, invasion and radioresistance in glioblastoma (GB). Pharmacological targeting is difficult as many in vitro-effective agents are not suitable for in patient applications. We aimed to develop a method to test the well tolerated AMPAR- and NMDAR-antagonist xenon gas as a radiosensitizer in GB. METHODS: We designed a diffusion-based system to perform the colony formation assay (CFA), the radiobiological gold standard, under xenon exposure. Stable and reproducible gas atmosphere was validated with oxygen and carbon dioxide as tracer gases. After checking for AMPAR and NMDAR expression via immunofluorescence staining we performed the CFA with the glioblastoma cell lines U87 and U251 as well as the non-glioblastoma derived cell line HeLa. Xenon was applied after irradiation and additionally tested in combination with NMDAR antagonist memantine. RESULTS: The gas exposure system proved compatible with the CFA and resulted in a stable atmosphere of 50% xenon. Indications for the presence of glutamate receptor subunits were present in glioblastoma-derived and HeLa cells. Significantly reduced clonogenic survival by xenon was shown in U87 and U251 at irradiation doses of 4-8 Gy and 2, 6 and 8 Gy, respectively (p < 0.05). Clonogenic survival was further reduced by the addition of memantine, showing a significant effect at 2-8 Gy for both glioblastoma cell lines (p < 0.05). Xenon did not significantly reduce the surviving fraction of HeLa cells until a radiation dose of 8 Gy. CONCLUSION: The developed system allows for testing of gaseous agents with CFA. As a proof of concept, we have, for the first time, unveiled indications of radiosensitizing properties of xenon gas in glioblastoma.

Assembling Au8 clusters on surfaces of bifunctional nanoimmunomodulators for synergistically enhanced low dose radiotherapy of metastatic tumor.

BACKGROUND: Radiotherapy is one of the mainstays of cancer therapy and has been used for treating 65-75% of patients with solid tumors. However, radiotherapy of tumors has two limitations: high-dose X-rays damage adjacent normal tissue and tumor metastases cannot be prevented. RESULTS: Therefore, to overcome the two limitations of radiotherapy, a multifunctional core-shell R837/BMS@Au8 nanoparticles as a novel radiosensitizer were fabricated by assembling Au8NCs on the surface of a bifunctional nanoimmunomodulator R837/BMS nanocore using nanoprecipitation followed by electrostatic assembly. Formed R837/BMS@Au8 NP composed of R837, BMS-1, and Au8 clusters. Au8NC can enhance X-ray absorption at the tumor site to reduce X-ray dose and releases a large number of tumor-associated antigens under X-ray irradiation. With the help of immune adjuvant R837, dendritic cells can effectively process and present tumor-associated antigens to activate effector T cells, meanwhile, a small-molecule PD-L1 inhibitor BMS-1 can block PD-1/PD-L1 pathway to reactivate cytotoxic T lymphocyte, resulting in a strong systemic antitumor immune response that is beneficial for limiting tumor metastasis. According to in vivo and in vitro experiments, radioimmunotherapy based on R837/BMS@Au8 nanoparticles can increase calreticulin expression on of cancer cells, reactive oxygen species generation, and DNA breakage and decrease colony formation. The results revealed that distant tumors were 78.2% inhibited depending on radioimmunotherapy of primary tumors. Therefore, the use of a novel radiosensitizer R837/BMS@Au8 NPs realizes low-dose radiotherapy combined with immunotherapy against advanced cancer. CONCLUSION: In conclusion, the multifunctional core-shell R837/BMS@Au8 nanoparticles as a novel radiosensitizer effectively limiting tumor metastasis and decrease X-ray dose to 1 Gy, providing an efective strategy for the construction of nanosystems with radiosensitizing function.

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.

Evidence for the use of curcumin in radioprotection and radiosensitization.

Curcumin has antineoplastic properties and is considered a chemotherapeutic and chemopreventive agent. Curcumin may be associated with radiation therapy (RT) as a radiosensitizer for cancer cells and a radioprotector for normal cells. In principle, it may result in a reduction of RT dosage for the same therapeutic effect on cancer cells, and further reduced damage to normal cells. Though the overall level of evidence is modest, limited to in vivo and in vitro experiences and practically no clinical trials, as the risks of adverse effects are extremely low, it is reasonable to promote the general supplementation with curcumin during RT targeting the reduction of side effects through anti-inflammatory mechanisms.