high-Z Nanoparticles Research Articles

A novel approach to double-strand DNA break analysis through γ-H2AX confocal image quantification and bio-dosimetry.

DNA damage occurs in all living cells. γ-H2AX imaging by fluorescent microscopy is widely used across disciplines in the analysis of double-strand break (DSB) DNA damage. Here we demonstrate a method for the quantitative analysis of such DBSs. Ionising radiation, well known to induce DSBs, is used in this demonstration, and additional DBSs are induced if high-Z nanoparticles are present during irradiation. As a deliberate test of the methodology, cells are exposed to a spatially fractionated ionising radiation field, characterised by regions of high and low absorbed radiation dose that are only ever qualitatively verified biologically via γ-H2AX imaging. Here we validate our bio-dosimetric quantification method using γ-H2AX assays in the assessment of DSB enhancement. Our method reliably quantifies DSB enhancement in cells when exposed to either a spatially contiguous or fractionated irradiation fields. Using the γ-H2AX assay, we deduce the biological dose response, and for the first time, demonstrate equivalence to the independently measured physical absorbed dose. Using our novel method, we are also able quantify the nanoparticle DSB enhancement at the cellular level, which is not possible using physical dose measurement techniques. Our method therefore provides a new paradigm in γ-H2AX image quantification of DSBs, as well as an independently validated bio-dosimetry technique.

Significance of the proton energy loss mechanism to gold nanoparticles in proton therapy: a Geant4 simulation

The biological effectiveness in proton therapy is only slightly greater than of the treatment by X-ray and hence, many researches have suggested the use of gold nanoparticles for increasing the ionization interactions to produce more secondary electrons and elevate the yield of DNA damage. But the ionization interactions also lead to protons energy loss inside the nanoparticles. The present study shows that, the protons slowed-down by High-Z nanoparticles are responsible for dose enhancement rather than the produced secondary electrons. To this purpose, using Geant4 Monte Carlo tool, one million nanoparticles distributed in a proton irradiated volume and variation of the proton’s spectra and the dose related to this variation has been demonstrated. It was found that, the elevation in proton’s LET values when passing through the gold nanoparticles will lead to a more significant dose enhancement than the increased dose due to the extra secondary electrons. Also, it was found that, the mechanism of protons slowing-down by gold nanoparticles has another useful aspect in proton therapy in which, the dose leakage to surrounding healthy tissues will be reduced which must be considered in future investigations more precisely.

Enhancing radiotherapy for melanoma: the promise of high-Z metal nanoparticles in radiosensitization.

Melanoma is a type of skin cancer that can be challenging to treat, especially in advanced stages. Radiotherapy is one of the main treatment modalities for melanoma, but its efficacy can be limited due to the radioresistance of melanoma cells. Recently, there has been growing interest in using high-Z metal nanoparticles (NPs) to enhance the effectiveness of radiotherapy for melanoma. This review provides an overview of the current state of radiotherapy for melanoma and discusses the physical and biological mechanisms of radiosensitization through high-Z metal NPs. Additionally, it summarizes the latest research on using high-Z metal NPs to sensitize melanoma cells to radiation, both in vitro and in vivo. By examining the available evidence, this review aims to shed light on the potential of high-Z metal NPs in improving radiotherapy outcomes for patients with melanoma.

Investigating polyurethane foam loaded with high-z nanoparticles for gamma radiation shielding compared to Monte Carlo simulations

Since the beginning of research into radiation and protection against it, the importance of searching for proper materials against radiation hazards has been recognized. Gamma radiation protection materials usually deal with heavy elements with high prices, which are hard to maintain. Polyurethane-based (PU) materials are popular in sound and thermal insulation due to, their low-weight properties and, most importantly, fast and convenient construction ingredients. PU foams (PUF) can be used as radiation shield and noise and heat resistance due to their approachability, light-weight, high resistance, and comfortable construction. This study involved simulation and an experiment to construct and investigate the properties of Polyurethane material doped with lead oxide as a gamma shield. The shield was considered in several weight fractions of lead, yielding several samples. The MCNPX 2.6 Monte Carlo code has been utilized for simulation procedure, and 137Cs was employed as the gamma source in both simulation and experiment. The results offer a promising response against the gamma radiation and are suitable for attenuating gamma rays.

Ag-Pt@BSA bimetallic nanoparticles for breast cancer radiation treatment dose augmentation

Cancer has traditionally been treated with surgery and chemotherapy. Radiation therapy (RT) is a branch of oncology based on radiation therapy that can be used alone or in combination with surgery and chemotherapy to achieve local control of breast cancer. Radiosensitizers make tumor cells more responsive and sensitive to ionizing radiation, consequently facilitating production of free radicals and hastening DNA damages. Stages I to III of breast cancer is managed with curative intent with multimodality treatment including radiotherapy. The current cancer therapies in particular radiotherapy have a high risk of serious side effects to the healthy tissues and do not guarantee remission. In response to this challenge, the present study developed bovine serum albumin capped platinum and silver nanoparticles (Ag-Pt@BSA NPs), a bimetallic radiosensitizer, which is a remedy to the aforementioned issue. This research makes use of a nanoplatform that contains two high-Z nanoparticles— Pt and Ag. A variety of methods were used to fully characterize the developed Ag-Pt@BSA NPs. Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), UV–Vis, X-ray diffractometery (XRD) and energy-dispersive X-ray spectroscopy (EDS) techniques were used to investigate the physical and chemical features of designed bimetallic nanoradiosensitizer. The Ag-Pt@BSA naoradiosensitizer was proven to have successfully prepared by FTIR, XRD and EDX. According to the DLS result, the hydrodynamic size of the NPs is 35.42 nm, and the average diameter in the TEM image is around 7.8 ± 2.6 nm. The initial hydrodynamic size Ag-Pt@BSA was around 35 nm and within the storage time its size remained below 40 nm which indicating the unique colloidal stability of fabricated nanoradiosensitizers. The zeta potential of Ag-Pt@BSA radio-enhancement was determined to be approximately −17.9 mV, providing additional support for the nanoparticles’ colloidal stability. The results showed that the utilization of Ag-Pt@BSA NPs in conjunction with X-ray irradiation could substantially enhance the effectiveness of cancer therapy. This is supported by research, examining a series of in vitro tests including reactive oxygen species generation (ROS), cell viability, apoptosis and colony formation assay. Furthermore, the dosage-dependent radiosensitizing ability of the Ag-Pt@BSA NPs was also observed in the apoptosis and MTT assay against 4 T1 cells by increasing the localized radiation dosage. Ag-Pt@BSA NPs could be a potential radio-enhancer agent against breast cancers and, by extension, other cancers, since it multiplies the therapeutic effect of low-dose radiation while reducing the damage to normal tissues compared to high-dose radiation therapy. Increasing the concentration of Ag-Pt@BSA NPs and the dosage of X-ray irradiation boosted the radiosensitizing capacity in a dose-dependent way.

Application of High-Z Nanoparticles to Enhance Current Radiotherapy Treatment.

Radiotherapy is an essential component of the treatment regimens for many cancer patients. Despite recent technological advancements to improve dose delivery techniques, the dose escalation required to enhance tumor control is limited due to the inevitable toxicity to the surrounding healthy tissue. Therefore, the local enhancement of dosing in tumor sites can provide the necessary means to improve the treatment modality. In recent years, the emergence of nanotechnology has facilitated a unique opportunity to increase the efficacy of radiotherapy treatment. The application of high-atomic-number (Z) nanoparticles (NPs) can augment the effects of radiotherapy by increasing the sensitivity of cells to radiation. High-Z NPs can inherently act as radiosensitizers as well as serve as targeted delivery vehicles for radiosensitizing agents. In this work, the therapeutic benefits of high-Z NPs as radiosensitizers, such as their tumor-targeting capabilities and their mechanisms of sensitization, are discussed. Preclinical data supporting their application in radiotherapy treatment as well as the status of their clinical translation will be presented.

Gold nanoparticles spectral CT imaging and limit of detectability in a new materials contrast-detail phantom

This study involves the synthesis, characterization, and spectral photon counting CT (SPCCT) imaging of gold nanoparticles tailored for enhancing the contrast of small cancer lesions. We used the modified Turkevich method to produce thiol-capped gold nanoparticles (AuNPs) at different concentrations (20, 15, 10, 5, 2.5, 1.25, 0.6 mg/ml). We thoroughly characterized the AuNPs using Transmission Electron Microscopy (TEM), X-ray diffraction spectroscopy (XRD), Dynamic Light Scattering (DLS), and UV–visible absorption spectroscopy. To assess the AuNPs contrast enhancing performance, we designed and built a new material contrast detail phantom for CT imaging and determined the minimum detectable concentrations of AuNPs in simulated lesions of small diameters (1, 2, 3, and 5 mm). The synthesized AuNPs are spherical with an average size of approximately 20 ± 4 nm, with maximum UV absorption occurring at 527 nm wavelength, and exhibit a face-centered cubic structure of gold according to XRD analysis. The synthesized gold nanoparticles demonstrated high contrast in SPCCT, suggesting their potential as contrast agents for imaging cancer tissues. The AuNPs image contrast was directly proportional to the AuNPs concentration. We are the first to determine that the lowest visually distinguishable contrast was achieved at a gold concentration of 5 mg/ml for a 2 mm simulated lesion. For 1 mm size lesion the smallest visible concentration was 10 mg/ml. This newly developed phantom can be used for determining the minimal concentration required for various high-Z nanoparticles to produce detectable contrast in X-ray imaging for small-size simulated lesions.

Utility of realistic microscopy-based cell models in simulation studies of nanoparticle-enhanced photon radiotherapy

To enhance the effect of radiation on the tumor without increasing the dose to the patient, the combination of high-Z nanoparticles with radiotherapy has been proposed. In this work, we investigate the effects of the physical parameters of nanoparticles (NPs) on the Dose Enhancement Factor (DEF), and on the Sensitive Enhancement Ratio (SER) by applying a version of the Linear Quadratic Model. A method for constructing voxelized realistic cell geometries in Monte Carlo simulations from confocal microscopy images was developed and applied to Gliobastoma Multiforme cell lines (U87 and U373). The comparison of simulations with realistic geometry and spherical geometry shows that there is significant impact on the survival curves obtained for the same irradiation conditions. Using this model, the DEF and the SER are determined as a function of the concentration, size and distribution of gold nanoparticles within the cell. For small NPs, d AuNP = 10 nm, no clear trend in the DEF and SER was observed when the number of NPs within the cell increases. Experimentally, the variable number of NPs measured inside the U373 cells (ranging between 1.48 × 105 and 1.19 × 106) also did not influence much the observed cell survival upon irradiation of the cells with a Co-60 source. The same lack of trend is obtained when the Au content in the cell is kept constant, 0.897 mg/g, but the size of the NPs is changed. However, if the number of NPs is kept constant (7.91 × 105) and the size changes, there is a critical diameter above which the dose effect increases significantly. Using the realistic geometries, it was verified that the key parameter for the DEF and the SER enhancement is the volume fraction of Au in the cell, with NP size being a more important parameter than the number of NPs.

Synthesis and Bioapplication of Emerging Nanomaterials of Hafnium.

A significant amount of progress in nanotechnology has been made due to the development of engineered nanoparticles. The use of metallic nanoparticles for various biomedical applications has been extensively investigated. Biomedical research is highly focused on them because of their inert nature, nanoscale structure, and similar size to many biological molecules. The intrinsic characteristics of these particles, including electronic, optical, physicochemical, and surface plasmon resonance, that can be altered by altering their size, shape, environment, aspect ratio, ease of synthesis, and functionalization properties, have led to numerous biomedical applications. Targeted drug delivery, sensing, photothermal and photodynamic therapy, and imaging are some of these. The promising clinical results of NBTXR3, a high-Z radiosensitizing nanomaterial derived from hafnium, have demonstrated translational potential of this metal. This radiosensitization approach leverages the dependence of energy attenuation on atomic number to enhance energy-matter interactions conducive to radiation therapy. High-Z nanoparticle localization in tumor issue differentially increases the effect of ionizing radiation on cancer cells versus nearby healthy ones and mitigates adverse effects by reducing the overall radiation burden. This principle enables material multifunctionality as contrast agents in X-ray-based imaging. The physiochemical properties of hafnium (Z = 72) are particularly advantageous for these applications. A well-placed K-edge absorption energy and high mass attenuation coefficient compared to elements in human tissue across clinical energy ranges leads to significant attenuation. Chemical reactivity allows for variety in nanoparticle synthesis, composition, and functionalization. Nanoparticles such as hafnium oxide exhibit excellent biocompatibility due to physiochemical inertness prior to incidence with ionizing radiation. Additionally, the optical and electronic properties are applicable in biosensing, optical component coatings, and semiconductors. The wide interest has prompted extensive research in design and synthesis to facilitate property fine-tuning. This review summarizes synthetic methods for hafnium-based nanomaterials and applications in therapy, imaging, and biosensing with a mechanistic focus. A discussion and future perspective section highlights clinical progress and elaborates on current challenges. By focusing on factors impacting applicational effectiveness and examining limitations this review aims to support researchers and expedite clinical translation of future hafnium-based nanomedicine.

High-Z Nanoparticle Tagging in Cryo-STEM for Localisation in Cryo-ET: Theory and Damage

High-Z Nanoparticle Tagging in Cryo-STEM for Localisation in Cryo-ET: Theory and Damage

Understanding the Role of Radio-Sensitizing Nanoparticles in Enhancing Pathologic Response in Soft Tissue Sarcomas

High-atomic-number (Z) nanoparticles produce a cascade of low-energy secondary electrons and characteristic X-rays when ionized by X-ray irradiation. These secondary particles deposit their energy in the vicinity of the nanoparticles and, provided that the latter are selectively accumulated within tumor cells, this results in increased DNA damage and tumor cell deaths. This study reviews the utilization of high-Z nanoparticles in the treatment of soft tissue sarcomas (STS). Both in vitro and in vivo experiments demonstrated that the dose is enhanced by approximately 1.2 when polyethelyne glycol (PEG)-modified gold nanoparticles, and from 1.4 to 1.8 when hafnium oxide nanoparticles (NBTXR3, Nanobiotix SA, France) are introduced into tumor cells and activated by X-ray beams. In a phase 2/3 clinical trial investigating the therapeutic benefit of using nanoparticles in preoperative external beam radiotherapy for locally advanced STS, the proportion of patients with a pathological complete response in their resected tumor was doubled when NBTXR3 nanoparticles were used. Additionally, a higher percentage of patients with complete tumor resection was observed in the NBTXR3 plus radiotherapy group. Similar toxicity profiles were found for both the NBTXR3 plus radiotherapy and the radiotherapy alone patient groups. The incorporation of radio-sensitizing nanoparticles in the preoperative radiotherapy of STS could enhance treatment outcomes.

Investigation of the anisotropic distribution of microdosimetric quantities in the vicinity of X-ray-irradiated gold nanoparticles

High-Z nanoparticles incorporated in tumors have great potential to enhance radiotherapy treatments by increasing the absorbed radiation dose in the vicinity of the nanoparticle. However, current Monte Carlo simulations estimate dose enhancement metrics in 1D, neglecting the anisotropy of the energy deposition around the nanoparticle. This could have radiobiological consequences and affect treatment accuracy. Accurate knowledge of the spatial distribution of the dose or other microdosimetric quantities is necessary for predicting radiobiological outcomes using biophysical models. In this study, we utilized a new combination of two Monte Carlo Variance Reduction Techniques (VRTs) to estimate microdosimetric quantities at the nanoscale, taking into account the anisotropy of the microdosimetric distributions. Our results show significant anisotropy in multi-events frequency-mean specific energy, as well as in microdosimetric distributions. These findings highlight the importance of considering anisotropy in microdosimetric distributions when predicting radiobiological outcomes and suggest that current 1D simulations may not accurately represent the real microdosimetric effects. Our work contributes to the development of multiscale dosimetry approaches for radiotherapy treatments with high-Z nanoparticles.

Nanoscale Hafnium Metal-Organic Frameworks Enhance Radiotherapeutic Effects by Upregulation of Type I Interferon and TLR7 Expression.

Recent preclinical and clinical studies have highlighted the improved outcomes of combination radiotherapy and immunotherapy. Concurrently, the development of high-Z metallic nanoparticles as radiation dose enhancers has been explored to widen the therapeutic window of radiotherapy and potentially enhance immune activation. In this study, folate-modified hafnium-based metal-organic frameworks (HfMOF-PEG-FA) are evaluated in combination with imiquimod, a TLR7 agonist, as a well-defined interferon regulatory factor (IRF) stimulator for local antitumor immunotherapy. The enhancement of radiation dose deposition by HfMOF-PEG-FA and subsequent generation of reactive oxygen species (ROS) deregulates cell proliferation and increases apoptosis. HfMOF-PEG-FA loaded with imiquimod (HfMOF-PEG-FA@IMQ) increases DNA double-strand breaks and cell death, including apoptosis, necrosis, and calreticulin exposure, in response to X-ray irradiation. Treatment with this multipronged therapy promotes IRF stimulation for subsequent interferon production within tumor cells themselves. The novel observation is reported that HfMOF itself increases TLR7 expression, unexpectedly pairing immune agonist and receptor upregulation in a tumor intrinsic manner, and supporting the synergistic effect observed with the γH2AX assay. T-cell analysis of CT26 tumors following intratumoral administration of HfMOF-PEG-FA@IMQ with radiotherapy reveals a promising antitumor response, characterized by an increase in CD8+ and proliferative T cells.

A Monte Carlo study of the dose enhancement effects of high-z foils in proton therapy

AbstractBackground:This investigation quantifies the dose enhancement effect and dose distribution modifications due to the presence of high-z nanospheres in a proton beam.Methods:Various proton pencil beams of therapeutic energies (60–226 MeV) and spatial distribution of 2·7 mm spot size diameter were simulated onto a water phantom utilising the TOPAS Monte Carlo toolkit version 3.6.1. The simulation modelled either water or nanospheres of high-z materials (gold, silver or platinum) at the location of the Bragg Peak (BP) to compare the differences of the resulting dose distributions.Results:The introduction of the nanospheres increases the maximum dose, narrows the BP and shifts the BP location upstream compared to the water phantom with no nanospheres.Conclusions:This work shows that the local dose can be enhanced with the use of high-z nanoparticles in proton therapy, thereby increasing patient safety and decreasing side effects with the same amount of delivered radiation.

Prospects of nanoparticle-based radioenhancement for radiotherapy.

Radiotherapy is a key pillar of solid cancer treatment. Despite a high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs at risk and subsequent normal tissue toxicities. Nanotechnology offers an attractive opportunity for increasing the efficacy and safety of cancer radiotherapy. Leveraging the freedom of design and the growing synthetic capabilities of the nanomaterial-community, a variety of engineered nanomaterials have been designed and investigated as radiosensitizers or radioenhancers. While research so far has been primarily focused on gold nanoparticles and other high atomic number materials to increase the absorption cross section of tumor tissue, recent studies are challenging the traditional concept of high-Z nanoparticle radioenhancers and highlight the importance of catalytic activity. This review provides a concise overview on the knowledge of nanoparticle radioenhancement mechanisms and their quantification. It critically discusses potential radioenhancer candidate materials and general design criteria for different radiation therapy modalities, and concludes with research priorities in order to advance the development of nanomaterials, to enhance the efficacy of radiotherapy and to increase at the same time the therapeutic window.

Treatment planning with a 2.5MV photon beam for radiation therapy.

The shallow depth of maximum dose and higher dose fall-off gradient of a 2.5MV beam along the central axis that is available for imaging on linear accelerators is investigated for treatment of shallow tumors and sparing the organs at risk (OARs) beyond it. In addition, the 2.5MV beam has an energy bridging the gap between kilo-voltage (kV) and mega-voltage (MV) beams for applications of dose enhancement with high atomic number (Z) nanoparticles. We have commissioned and utilized a MATLAB-based, open-source treatment planning software (TPS), matRad, for intensity-modulated radiation therapy (IMRT) dose calculations. Treatment plans for prostate, liver, and head and neck (H&N), nasal cavity, two orbit cases, and glioblastoma multiforme (GBM) were performed and compared to a conventional 6MV beam. Additional Monte Carlo calculations were also used for benchmarking the central axis dose. Both beams had similar planning target volume (PTV) dose coverage for all cases. However, the 2.5MV beam deposited 6%-19% less integral doses to the nasal cavity, orbit, and GBM cases than 6MV photons. The mean dose to the heart in the liver plan was 10.5% lower for 2.5MV beam. The difference between the doses to OARs of H&N for two beams was under 3%. Brain mean dose, brainstem, and optic chiasm max doses were, respectively, 7.5%-14.9%, 2.2%-8.1%, and 2.5%-19.0% lower for the 2.5MV beam in the nasal cavity, orbit, and GBM plans. This study demonstrates that the 2.5MV beam can produce clinically relevant treatment plans, motivating future efforts for design of single-energy LINACs. Such a machine will be capable of producing beams at this energy beneficial for low- and middle-income countries, and investigations on dose enhancement from high-Z nanoparticles.

Pharmacokinetics derived from PET imaging of inspiring radio-enhancer platinum nanoparticles

Personalized medicine approach in radiotherapy requires the delivery of precise dose to the tumor. The concept is to increase the effectiveness of radiotherapy while sparing the surrounding heathy tissue. This can be achieved by the use of high-Z metal-based nanoparticles (NPs) as radio-enhancers and PET imaging for mapping NPs distribution to guide the irradiation. In the present study, radio-enhancing platinum NPs were radiolabeled and imaged to assess their pharmacokinetics over time. PET imaging of these NPs revealed high enhanced permeation and retention effect. The maximal tumor accumulation (4.8 ± 0.8 %ID/cc) was observed at 24 h post-injection along with persistent accumulation of the NPs, especially at the tumor ring, even after several days. These properties positively suggest the potential clinical use of these NPs.

DSB and SSB damages by 0.1–20 MeV protons enhanced by high-Z nanoparticles computed using Geant4-DNA

The interaction of protons in the energy range of 0.1 to 20 MeV with water sphere, as the target volume, containing DNA molecules has been simulated using Geant4-DNA toolkit. PDB format of DNA was used as DNA molecules were distributed randomly inside the target volume. The number of DNA damage is calculated in the absence of nanoparticles. Then the simulation has been repeated in the presence of 3 different nanoparticles (gold, gadolinium and iodine), in the identical physical and geometric conditions. The number of DNA damages without nanoparticles was in agreement with previous studies. Simulations results demonstrate that adding gold nanoparticles leads to increase damage yields in DNA. Increase of the yield between 10% to 50% were observed for SSB and DSB. Enhancement of the yield damage in the case of gadolinium and iodine nanoparticles was observed to be 4% and 9% less than that of gold nanoparticles.

Bismuth Nanoparticle and Polyhydroxybutyrate Coatings Enhance the Radiopacity of Absorbable Inferior Vena Cava Filters for Fluoroscopy-Guided Placement and Longitudinal Computed Tomography Monitoring in Pigs.

Inferior vena cava filters (IVCFs) constructed with poly-p-dioxanone (PPDO) are promising alternatives to metallic filters and their associated risks and complications. Incorporating high-Z nanoparticles (NPs) improves PPDO IVCFs' radiopacity without adversely affecting their safety or performance. However, increased radiopacity from these studies are insufficient for filter visualization during fluoroscopy-guided PPDO IVCF deployment. This study focuses on the use of bismuth nanoparticles (BiNPs) as radiopacifiers to render sufficient signal intensity for the fluoroscopy-guided deployment and long-term CT monitoring of PPDO IVCFs. The use of polyhydroxybutyate (PHB) as an additional layer to increase the surface adsorption of NPs resulted in a 2-fold increase in BiNP coating (BiNP-PPDO IVCFs, 3.8%; BiNP-PPDO + PHB IVCFs, 6.2%), enabling complete filter visualization during fluoroscopy-guided IVCF deployment and, 1 week later, clot deployment. The biocompatibility, clot-trapping efficacy, and mechanical strength of the control PPDO (load-at-break, 6.23 ± 0.13 kg), BiNP-PPDO (6.10 ± 0.09 kg), and BiNP-PPDO + PHB (6.15 ± 0.13 kg) IVCFs did not differ significantly over a 12-week monitoring period in pigs. These results indicate that BiNP-PPDO + PHB can increase the radiodensity of a novel absorbable IVCF without compromising device strength. Visualizing the device under conventional radiographic imaging is key to allow safe and effective clinical translation of the device.

Nanostructures as Radionuclide Carriers in Auger Electron Therapy.

The concept of nanoparticle-mediated radionuclide delivery in the cancer treatment has been widely discussed in the past decade. In particular, the use of inorganic and organic nanostructures in the development of radiopharmaceuticals enables the delivery of medically important radioisotopes for radionuclide therapy. In this review, we present the development of nanostructures for cancer therapy with Auger electron radionuclides. Following that, different types of nanoconstructs that can be used as carriers for Auger electron emitters, design principles, nanoparticle materials, and target vectors that overcame the main difficulties are described. In addition, systems in which high-Z element nanoparticles are used as radionuclide carriers, causing the emission of photoelectrons from the nanoparticle surface, are presented. Finally, future research opportunities in the field are discussed as well as issues that must be addressed before nanoparticle-based Auger electron radionuclide therapy can be transferred to clinical use.