Radiosensitizer For Radiotherapy Research Articles

State-of-the-art application of nanoparticles in radiotherapy: aplatform for synergistic effects in cancer treatment.

Radiotherapy (RT) is agold standard cancer treatment worldwide. However, RT has limitations and many side effects. Nanoparticles (NPs) have exclusive properties that allow them to be used in cancer therapy. Consequently, the combination of NP and RT opens up anew frontier in cancer treatment. Among NPs, gold nanoparticles (GNPs) are the most extensively studied and are considered ideal radiosensitizers for radiotherapy due to their unique physicochemical properties and high X‑ray absorption. This review analyzes the various roles of NPs as radiosensitizers in radiotherapy of glioblastoma (GBS), prostate cancer, and breast cancer and summarizes recent advances. Furthermore, the underlying mechanisms of NP radiosensitization, including physical, chemical, and biological mechanisms, are discussed, which may provide new directions for next-generation GNP optimization and clinical transformation.

In Vitro and In Vivo Synergetic Radiotherapy with Gold Nanoparticles and Docetaxel for Pancreatic Cancer.

This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 μg/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% (p = 0.05) decrease in spheroid size and a 45% (p = 0.05) increase in DNA DSBs. In vivo results showed a 20% (p = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects.

Monte Carlo study on nanogold dose enhancement for breast radiotherapy using an ICRP female computational phantom

Due to distinct photoelectric absorption properties and physiochemical features, high-atomic-element nanomaterials are frequently used as radiosensitizer for radiotherapy, such as gold nanoparticles. which in-turn can increase radiation dose to tumours while minimizing exposure to normal tissues. The aim of this study is to investigate the dose enhancement due to the presence of nanogold particles mixed with breast tissue using a real radiotherapy plan with two photon energies, with and without flattening filter. A fully validated linac head was used to model a complete field-in-field (FIF) radiotherapy breast plan using 4 and 6 MV with a flattening filter (FF) and flattening filter-free (FFF) using BEAMnrc/EGSnrc MC code. The dose distributions were simulated in a female ICRP voxel computational phantom. The dose enhancement ratio (DER) and flattening filter-free enhancement ratio (FFFER) were calculated for a range of nanogold concentrations. The results showed that the DER increased with increasing nanogold concentration. The maximum DER was achieved when FFF was used and the increase was higher for 4 MV than 6 MV. The FFFER was higher for the 4 MV beam than 6 MV when 40 mg/ml nanogold was used. The combination of higher nanogold concentrations, lower photon energies, and FFF resulted in a higher dose enhancement. The implementation of nanogold particles in breast tissue enhanced the dose deposition, especially with FFF, as presented in this study. The results would improve nanogold-enhanced breast radiotherapy and dose delivery with an increase in patient throughput.

Biodegradable hafnium-doped CaCO3 nanoparticles as a dual-modality radiosensitizer for cancer radiotherapy.

Aim: Radiotherapy employs high-energy ionizing radiation to inflict DNA damage on cancer cells, thereby causing their demise. However, this procedure can inadvertently harm healthy tissue. Thus, thisstudy aimed to develop biodegradable radiosensitizers that counteract these adverse effects by enhancing the radiation sensitivity of tumor cells and safeguarding normal cells.Materials & methods: A biodegradable radiosensitizer was engineered by incorporating hafnium ions (Hf) into calcium carbonate (CaCO3) nanoparticles via a chemical precipitation technique, resulting in the formation of Hf:CaCO3 nanoparticles.Results & conclusion: Our findings demonstrate that Hf:CaCO3 nanoparticles exhibit pH-dependent solubility and can augment the efficacy of radiotherapy in treating cancer cells. This research underscores the potential of Hf:CaCO3 nanoparticles as a dual-modality radiosensitizer in radiotherapy.

Analysis of Novel Schiff Base-Fe Complexes Against Breast Cancer Cells’ Viability

Two potential novels Schiff base iron (Fe) complexes Fe-L2 and Fe-L3 (where L2= N, N'-bis (o-hydroxyacetophenone) ethylenediamine and L3= N, N'-bis (o-hydroxybenzaldehyde) phenylenediamine) were synthesized from interaction a hot methanolic solution of each ligand L2 or L3 (0.01mole) with the appropriate amount of Fe (NO3)3.9H2O metal salt (0.01mole). This study investigated the cytotoxicity induced by both complexes (0.1 to 100 µg/ml) in MCF-7 and MDA-MB 231 cell lines. After 24 hours of treatment, the cell viabilities of both MCF-7 and MDA-MB-231 cells were linearly proportional to the Fe-L2 concentrations. A higher concentration of Fe-L2 would cause higher cell killings. On the other hand, most of the Fe-L3 concentrations caused total cell deaths for both cell lines, except for the lowest concentration (0.1 µg/ml). Fe-L2 and Fe-L3 also caused lower cell viability of MDA-MB-231 cells compared to MCF-7 cells. Overall, the obtained Fe-L3 is more toxic than Fe-L2 in breast cancer cells. It is suggested that the Fe-L3 is an excellent agent against breast cancer cells; meanwhile, the Fe-L2 is biocompatible and a good support in medical applications, especially as a radiosensitizer in radiotherapy.

Facile preparation of silver based radiosensitizers via biomineralization method for enhanced in vivo breast cancer radiotherapy

To solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag2S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2S@BSA to impart active targeting capability to the final formulation (Ag-Ag2S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet–visible spectroscopy (UV–Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy.

ALOX5 promotes esophageal squamous cell carcinoma radiosensitization by ferroptosis

ObjectiveTo investigate the role of lipid peroxidation and ferroptosis pathways in esophageal squamous cell carcinoma (SCC) and to provide some information for clinical treatment. MethodsIt is an experimental research. We detected the lipid peroxidation levels in esophageal SCC cells with or without ferrostatin-1 (Ferr-1), a ferroptosis inhibitor, by C11-BODIPY staining at irradiation doses ranging from 0 Gy to 6 Gy. Then, we investigated the effects of ionizing radiation (IR) and Ferr-1 on the clonogenic survival. The expression of lipoxygenase ALOX5 after IR in the presence or absence of Ferr-1 was examined by Western blot method. The expression of lipoxygenase ALOX5 was overexpressed or knocked down in esophageal SCC cells by RNA interference technique, respectively. Then changes in lipid peroxidation levels and clonogenic survival levels were detected again. ResultsThe data suggest that IR causes lipid peroxidation and ferroptotic death in esophageal SCC cells, and as part of the cell death response induced by IR. IR causes ferroptotic toxicity in part by increasing ALOX5. When the lipoxygenase ALOX5 was overexpressed, the level of death from lipid peroxidation and ferroptotic toxicity also increased. However, knockdown of the lipoxygenase ALOX5 suppressed IR-induced lipid peroxidation levels and ferroptotic toxicity in esophageal SCC cells. ConclusionWe found that IR causes lipid peroxidation and ferroptosis in esophageal SCC, while modulating the expression of ALOX5 could be used as a radiosensitizer for radiotherapy.

Amplifying "eat me signal" by immunogenic cell death for potentiating cancer immunotherapy.

Immunogenic cell death (ICD) is a unique mode of cell death, which can release immunogenic damage-associated molecular patterns (DAMPs) and tumor-associated antigens to trigger long-term protective antitumor immune responses. Thus, amplifying "eat me signal" during tumor ICD cascade is critical for cancer immunotherapy. Some therapies (radiotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), etc.) and inducers (chemotherapeutic agents, etc.) have enabled to initiate and/or facilitate ICD and activate antitumor immune responses. Recently, nanostructure-based drug delivery systems have been synthesized for inducing ICD through combining treatment of chemotherapeutic agents, photosensitizers for PDT, photothermal transformation agents for PTT, radiosensitizers for radiotherapy, etc., which can release loaded agents at an appropriate dosage in the designated place at the appropriate time, contributing to higher efficiency and lower toxicity. Also, immunotherapeutic agents in combination with nanostructure-based drug delivery systems can produce synergetic antitumor effects, thus potentiating immunotherapy. Overall, our review outlines the emerging ICD inducers, and nanostructure drug delivery systems loading diverse agents to evoke ICD through chemoradiotherapy, PDT, and PTT or combining immunotherapeutic agents. Moreover, we discuss the prospects and challenges of harnessing ICD induction-based immunotherapy, and highlight the significance of multidisciplinary and interprofessional collaboration to promote the optimal translation of this treatment strategy.

Evaluation of efficacy of tumor-specific nanoliposomal radiosensitizer in radiotherapy

Radiotherapy is one of the cancer treatment options in which ionizing radiation is used. While the ionizing radiation used here damages the tumor cells, it also damages the surrounding healthy cells and tissues. One of the approaches used to reduce the undesirable side effects and increase the therapeutic efficacy of radiotherapy is the use of radiosensitizers. Up to now, different radiosensitizers have been investigated for this purpose and recently, nanotechnology-based radiosensitizer research has attracted much attention. In this study, the therapeutic efficacy of tumor-targeted, nano-sized liposomal radiosensitizers containing quantum dots-photosensitizer conjugate was evaluated in vivo. It was aimed to destroy more tumor cells by using same the radiation doses routinely used in cancer treatment in radiation oncology clinics or to destroy about the same amount of tumor cells by using lower radiation doses than the routinely used clinical dose. For this purpose, nano-sized, PEG-coated, and folic acid-modified tumor-specific liposomes loaded with quantum dots (QD = CdSe/ZnS) - photosensitizer (Ce6 = Clorine-e6) conjugate was prepared and their therapeutic efficacy was evaluated in 4T1 murine breast cancer cell tumor-bearing mice. Following the single dose of 10Gy 6 MV X-ray irradiation after administration of liposomal radiosensitizer, changes in animals' weights and tumor volumes were measured and animal survival was monitored to evaluate the efficacy of the treatment. Histopathological studies were also performed to examine possible damage to the tumor and normal tissues. In control groups, only X-ray irradiation was applied or no treatment was applied to mice. The results showed that the liposomal radiosensitizer plus radiotherapy killed more cancer cells than radiotherapy alone. While tumor volumes increased in the control group, approximately a 39% reduction in tumor volumes was observed in mice treated with x-ray irradiation following administration of the liposomal radiosensitizer. The obtained results showed that nano-sized liposomal radiosensitizers could be a promising radiosensitizer to achieve better treatment efficacy in radiotherapy by applying fewer radiation doses compared to clinically used radiation doses.

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.

New Frontiers in Colorectal Cancer Treatment Combining Nanotechnology with Photo- and Radiotherapy.

Colorectal cancer is the third most common cancer worldwide. Despite recent advances in the treatment of this pathology, which include a personalized approach using radio- and chemotherapies in combination with advanced surgical techniques, it is imperative to enhance the performance of these treatments and decrease their detrimental side effects on patients' health. Nanomedicine is likely the pathway towards solving this challenge by enhancing both the therapeutic and diagnostic capabilities. In particular, plasmonic nanoparticles show remarkable potential due to their dual therapeutic functionalities as photothermal therapy agents and as radiosensitizers in radiotherapy. Their dual functionality, high biocompatibility, easy functionalization, and targeting capabilities make them potential agents for inducing efficient cancer cell death with minimal side effects. This review aims to identify the main challenges in the diagnosis and treatment of colorectal cancer. The heterogeneous nature of this cancer is also discussed from a single-cell point of view. The most relevant works in photo- and radiotherapy using nanotechnology-based therapies for colorectal cancer are addressed, ranging from in vitro studies (2D and 3D cell cultures) to in vivo studies and clinical trials. Although the results using nanoparticles as a photo- and radiosensitizers in photo- and radiotherapy are promising, preliminary studies showed that the possibility of combining both therapies must be explored to improve the treatment efficiency.

Multifaceted nanozymes for synergistic antitumor therapy: A review

Although various cancer therapies have been developed in the last decade, much of their anti-tumor effects are restricted by the tumor microenvironment complexity, such as the hypoxia in photodynamic therapy and sonodynamic therapy, and the poor penetration of radiosensitizers in radiotherapy. The development of multifunctional nanozymes that combines the physiochemical properties of nanomaterials (e.g. special optical transformation properties) and catalytic activities of enzymes (mainly including superoxide dismutase, catalase, peroxidase, and oxidase) can provide promising weapons for enhancing antitumor efficiency. Importantly, some types of nanozymes can also act as ideal nanocarriers for improving therapeutic reagent delivery, especially in tumor immunotherapy. In this review, we summarize the recent advances in multifunctional nanozymes with an emphasis on their applications in catalytic therapy combined with immunotherapy, phototherapy, sonodynamic therapy, radiotherapy, and chemotherapy. We believe this review will provide theoretical and technical support for the subsequent development of nanozyme-based antitumor reagents and inspire novel therapeutic strategies for efficient tumor therapy.

Evaluation of Bismuth Oxide Nanoparticles (BiONPs) as a Safe Radiobiological Enhancer for Breast Cancer Radiotherapy

Cancer incidence has been increasing over the years and it is the second leading cause of death globally [1]. The therapeutic strategies in killing the cancerous tissue while keeping the normal healthy tissue uninterrupted can be further improved by introducing nanoparticles (NPs) as radiosensitizers in radiotherapy. In pre-clinical research, a few nanoparticle elements had shown the potential to be radiosensitizers, such as gold, superparamagnetic iron oxide, platinum, and bismuth nanoparticles. Bismuth oxide nanoparticles (BiONPs) have been investigated as a potential radiosensitizer in radiotherapy due to their least toxic and biocompatibility properties. In addition, due to the presence of metallic nanoparticles in cells and their environment, more DNA damage will be introduced and thus enhance the radiation treatment efficacy.
 
 This research project was conducted to evaluate the potential of BiONPs to increase the radiation treatment in MCF-7 breast cancer cells and their side effects on the non-targeted breast cancer cells. BiONPs were synthesized through the hydrothermal method, as established in the previous study [2]. The treated and control cells in flasks were irradiated with radiation doses between 0 to 12 Gy at a constant dose rate of 300 cGy/minutes in the beam field size of 10 cm x 10 cm for a 6 MV photon beam, delivered with linear accelerator Primus model (Siemen Healthcare, USA). The irradiated cell-conditioned medium (ICCM) was collected from the targeted cells and transferred into the non-targeted cells. The cell viability assay was employed to evaluate the effect of BiONPs on directly irradiated and non-irradiated cells.
 
 In our prior work, the BiONPs had shown to boost radiosensitisation effects in treated cells compared to control cells, with a sensitisation enhancement ratio (SER) of 1.38 [3], as shown in Figure 1. The increased radiosensitisation effects might be attributed to the characteristics of BiONPs with a high effective atomic number (Z=83), which promotes radiation interaction, mainly radiation absorption and scattering. Meanwhile, the present study demonstrated that the non-irradiated MCF-7 cells could maintain their cell viability for more than 80% after 48 h incubation with ICCM treated with BiONPs at 2, 6, and 12 Gy. Furthermore, a comparable trend in cell viability was observed in non-irradiated MCF-7 cells for treated and control groups (p<0.05), as illustrated in Figure 2. This finding indicated that BiONPs are not harmful and do not contribute to side effects in non-targeted cells.
 The present works have provided evidence that using BiONPs as radiosensitizers in radiotherapy is safe and does not significantly introduce side effects in the non-targeted cells. These data proved the impacts of BiONPs as a potential tool for a safe radiobiological enhancer that will benefit future radiation therapy strategies in cancer management.

Natural Radiosensitizers in Radiotherapy: Cancer Treatment by Combining Ionizing Radiation with Resveratrol.

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.

Cellular analysis on the radiation induced bystander effects due to bismuth oxide nanoparticles with 6 MV photon beam radiotherapy

BackgroundThe therapeutic strategies in killing the cancerous tissue while keeping the normal healthy tissue uninterrupted can be further improved by introducing nanoparticles as radiosensitizer in radiotherapy. Nevertheless, healthy cells might still be affected by radiation-induced bystander effect (RIBE) response due the presence of nanoparticles. Thus, the potential negative effects in non-irradiated adjacent cells must be investigated. AimThe current study aims to explore the cellular effects of bismuth oxide nanoparticles (Bi2O3 NPs) on human breast cancer (MCF-7) and human foetal osteoblast (hFOB 1.19) cells due to the RIBE after irradiation with 6 MV clinical photon beam. Materials and methodsThe irradiated-cell conditioned medium (ICCM) treated with and without Bi2O3 NPs from the irradiated cells were collected and then transferred into the non-targeted cells. The ability of the bystander cells to proliferate and their ROS generation were analyzed. DNA status of the cells and the possibility of apoptosis were evaluated using FTIR spectroscopy and MUSE Cell Analyzer, respectively. ResultsThe current study revealed that MCF-7 and hFOB 1.19 bystander cells may continue to proliferate and survive following short and long-term incubation with ICCM treatment with Bi2O3 NPs. The survival rate of the treated bystander cells increased approximately 3%–8% compared to the untreated group. Although the bystander cells exhibited an increase in ROS and apoptosis, the addition of Bi2O3 NPs had no significant detrimental influence on the cells. Variation in the DNA vibrational amplitude detected by FTIR in bystander cells was less than 5% compared to the control group. ConclusionThis study discovered that the application of Bi2O3 NPs as a radiosensitizer did not give a negative impact on the bystander cells. This outcome may give an advantage to the application of Bi2O3 NPs as radiosensitizer in radiotherapy to enhance cancer cells death without introducing further detrimental effects to the non-targeted cells.

Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency.

Tumor immunotherapy is only effective in a fraction of patients due to a low response rate and severe side effects, and these challenges of immunotherapy in clinics can be addressed through induction of immunogenic cell death (ICD). ICD is elicited from many antitumor therapies to release danger associated molecular patterns (DAMPs) and tumor‐associated antigens to facilitate maturation of dendritic cells (DCs) and infiltration of cytotoxic T lymphocytes (CTLs). The process can reverse the tumor immunosuppressive microenvironment to improve the sensitivity of immunotherapy. Nanostructure‐based drug delivery systems (NDDSs) are explored to induce ICD by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) for photodynamic therapy (PDT), photothermal conversion agents for photothermal therapy (PTT), and radiosensitizers for radiotherapy (RT). These NDDSs can release loaded agents at a right dose in the right place at the right time, resulting in greater effectiveness and lower toxicity. Immunotherapeutic agents can also be combined with these NDDSs to achieve the synergic antitumor effect in a multi‐modality therapeutic approach. In this review, NDDSs are harnessed to load multiple agents to induce ICD by chemotherapy, PDT, PTT, and RT in combination of immunotherapy to promote the therapeutic effect and reduce side effects associated with cancer treatment.

Influence of PEG-coated Bismuth Oxide Nanoparticles on ROS Generation by Electron Beam Radiotherapy

Abstract Introduction: Nanoparticles (NPs) have been proven to enhance radiotherapy doses as radiosensitizers. The introduction of coating materials such as polyethylene glycol (PEG) to NPs could impact the NPs’ biocompatibility and their effectiveness as radiosensitizers. Optimization of surface coating is a crucial element to ensure the successful application of NPs as a radiosensitizer in radiotherapy. This study aims to investigate the influence of bismuth oxide NPs (BiONPs) coated with PEG on reactive oxygen species (ROS) generation on HeLa cervical cancer cell line. Material and methods: Different PEG concentrations (0.05, 0.10, 0.15 and 0.20 mM) were used in the synthesis of the NPs. The treated cells were irradiated with 6 and 12 MeV electron beams with a delivered dose of 3 Gy. The reactive oxygen species (ROS) generation was measured immediately after and 3 hours after irradiation. Results: The intracellular ROS generation was found to be slightly influenced by electron beam energy and independent of the PEG concentrations. Linear increments of ROS percentages over the 3 hours of incubation time were observed. Conclusions: Finally, the PEG coating might not substantially affect the ROS generated and thus emphasizing the functionalized BiONPs application as the radiosensitizer for electron beam therapy.

Hafnium-Based Metal-Organic Framework Nanoparticles as a Radiosensitizer to Improve Radiotherapy Efficacy in Esophageal Cancer.

Radiotherapy is one of the most widely used clinical treatments for tumors, but it faces limitations, such as poor X-ray retention at the tumor site. The use of radiosensitizers containing high Z elements is an effective way to enhance X-ray absorption. Here, we demonstrate a simple one-step method for the synthesis of UiO-66-NH2(Hf) metal–organic framework nanoparticles for use as radiosensitizers in radiotherapy. The UiO-66-NH2(Hf) nanoparticles had a diameter of less than 100 nm and were stable in the physiological environment. UiO-66-NH2(Hf) induced apoptosis by enhancing X-ray absorption, as confirmed by in vitro and in vivo experiments. These characteristics make UiO-66-NH2(Hf) a promising radiosensitizer for esophageal cancer radiotherapy.

Advances in antitumor nanomedicine based on functional metal-organic frameworks beyond drug carriers.

Nanoscale metal-organic frameworks (MOFs) have attracted widespread interest due to their unique properties including a tunable porous structure, high drug loading capacity, structural diversity, and outstanding biocompatibility. MOFs have been extensively explored as drug nanocarriers in biotherapeutics. However, by harnessing the functionality of ligands and metal ions or clusters in MOFs, the applications of MOFs can be extended beyond drug delivery vehicles. Based on the intrinsic properties of the components of MOFs (e.g. magnetic moments of metal ions and fluorescence of ligands), different imaging modes can be achieved with varied MOFs. With careful design of the composition of MOFs (e.g. modification of organic linkers), they can respond to tumor microenvironments to realize on-demand treatment. By incorporating porphyrin-based ligands (photosensitizers for photodynamic therapy) or high-Z metal ions (radiosensitizers for radiotherapy) into the scaffold of MOFs, MOFs themselves can act as anticancer therapeutic agents. In this review, we highlight the application of MOFs from the above-mentioned aspects and discuss the prospects and challenges for using MOFs in stimuli-responsive imaging-guided antitumor therapy.

DNA Dosimetry with Gold Nanoparticle Irradiated by Proton Beams: A Monte Carlo Study on Dose Enhancement

Heavy atom nanoparticles, such as gold nanoparticles, are proven effective radiosensitizers in radiotherapy to enhance the dose delivery for cancer treatment. This study investigated the effectiveness of cancer cell killing, involving gold nanoparticle in proton radiation, by changing the nanoparticle size, proton beam energy, and distance between the nanoparticle and DNA. Monte Carlo (MC) simulation (Geant4-DNA code) was used to determine the dose enhancement in terms of dose enhancement ratio (DER), when a gold nanoparticle is present with the DNA. With varying nanoparticle size (radius = 15–50 nm), distance between the gold nanoparticle and DNA (30–130 nm), as well as proton beam energy (0.5–25 MeV) based on the simulation model, our results showed that the DER value increases with a decrease of distance between the gold nanoparticle and DNA and a decrease of proton beam energy. The maximum DER (1.83) is achieved with a 25 nm-radius gold nanoparticle, irradiated by a 0.5 MeV proton beam and 30 nm away from the DNA.