A personalized Monte Carlo study of tumor and critical organ doses for trans-arterial radioembolization patients.

Trans-arterial radioembolization (TARE) is an intra-arterial treatment method for liver malignancies. In this procedure, the therapeutic tumor dose is significant for predicting the treatment effectiveness while the dose absorbed in an organ at risk provides an understanding of its tolerance to radiation. This study proposes a Monte Carlo (MC) approach for determining absorbed organ doses for patients undergoing TARE treatment. The technique is based on the use of a voxel-based partial body model generated for each patient from his/her anatomical image data to represent the critical body structures more realistically. These structures are first segmented from image slices to create an image block which is then incorporated into a radiation transport package (MCNP6.2) to perform MC simulations. When used along with the parameters specific to a patient's treatment, such as lung-shunt factor, tumor-to-normal liver ratio, fractional uptakes, and administered activity, this approach allowed more accurate simulation of radiation interactions and hence provided absorbed doses specific to a TARE patient. The MC method also calculated the absorbed doses in organs or tissues that were close to target tissues for which the Medical Internal Radiation Dose Committee (MIRD) formalism makes no predictions. MIRD calculations were found to overestimate the absorbed doses by as much as 11% in lungs, 5% in liver, and 20% in tumor volumes. This raises concerns about the treatment's efficacy when estimating the correct activity to be administered to a patient. When each patient simulation was repeated with a90Y source spectrum to reflect the distribution of varying beta energies, the liver and the lungs were observed to receive relatively lower doses than those obtained with monoenergetic beta particles. Thus, it can be stated that the approach adopted in this study offers a more precise model of the patient's critical tissues and serves as a personalized dosimetric tool for TARE treatment planning.

Preclinical Evaluation of a New Series of Albumin-Binding 177Lu-Labeled PSMA-Based Low-Molecular-Weight Radiotherapeutics.

Prostate-specific membrane antigen (PSMA)-based low-molecular-weight agents using beta(ß)-particle-emitting radiopharmaceuticals is a new treatment paradigm for patients with metastatic castration-resistant prostate cancer. Although results have been encouraging, there is a need to improve the tumor residence time of current PSMA-based radiotherapeutics. Albumin-binding moieties have been used strategically to enhance the tumor uptake and retention of existing PSMA-based investigational agents. Previously, we developed a series of PSMA-based, ß-particle-emitting, low-molecular-weight compounds. From this series, 177Lu-L1 was selected as the lead agent because of its reduced off-target radiotoxicity in preclinical studies. The ligand L1 contains a PSMA-targeting Lys-Glu urea moiety with an N-bromobenzyl substituent in the ε-amino group of Lys. Here, we structurally modified 177Lu-L1 to improve tumor targeting using two known albumin-binding moieties, 4-(p-iodophenyl) butyric acid moiety (IPBA) and ibuprofen (IBU), and evaluated the effects of linker length and composition. Six structurally related PSMA-targeting ligands (Alb-L1-Alb-L6) were synthesized based on the structure of 177Lu-L1. The ligands were assessed for in vitro binding affinity and were radiolabeled with 177Lu following standard protocols. All 177Lu-labeled analogs were studied in cell uptake and selected cell efficacy studies. In vivo pharmacokinetics were investigated by conducting tissue biodistribution studies for 177Lu-Alb-L2-177Lu-Alb-L6 (2 h, 24 h, 72 h, and 192 h) in male NSG mice bearing human PSMA+ PC3 PIP and PSMA- PC3 flu xenografts. Preliminary therapeutic ratios of the agents were estimated from the area under the curve (AUC0-192h) of the tumors, blood, and kidney uptake values. Compounds were obtained in >98% radiochemical yields and >99% purity. PSMA inhibition constants (Kis) of the ligands were in the ≤10 nM range. The long-linker-based agents, 177Lu-Alb-L4 and 177Lu-Alb-L5, displayed significantly higher tumor uptake and retention (p < 0.001) than the short-linker-bearing 177Lu-Alb-L2 and 177Lu-Alb-L3 and a long polyethylene glycol (PEG) linker-bearing agent, 177Lu-Alb-L6. The area under the curve (AUC0-192h) of the PSMA+ PC3 PIP tumor uptake of 177Lu-Alb-L4 and 177Lu-Alb-L5 were >4-fold higher than 177Lu-Alb-L2, 177Lu-Alb-L3, and 177Lu-Alb-L6, respectively. Also, the PSMA+ PIP tumor uptake (AUC0-192h) of 177Lu-Alb-L2 and 177Lu-Alb-L3 was ~1.5-fold higher than 177Lu-Alb-L6. However, the lowest blood AUC0-192h and kidney AUC0-192h were associated with 177Lu-Alb-L6 from the series. Consequently, 177Lu-Alb-L6 displayed the highest ratios of AUC(tumor)-to-AUC(blood) and AUC(tumor)-to-AUC(kidney) values from the series. Among the other agents, 177Lu-Alb-L4 demonstrated a nearly similar ratio of AUC(tumor)-to-AUC(blood) as 177Lu-Alb-L6. The tumor-to-blood ratio was the dose-limiting therapeutic ratio for all of the compounds. Conclusions: 177Lu-Alb-L4 and 177Lu-Alb-L6 showed high tumor uptake in PSMA+ tumors and tumor-to-blood ratios. The data suggest that linker length and composition can be modulated to generate an optimized therapeutic agent.

Experimental and computational study of the beta shielding properties of polycarbonate filled with lead nitrate.

The mass attenuation coefficient of lead nitrate (Pb(NO3)2)-filled polycarbonate (PC) composite films were determined both computationally (using Baltakmen's and Thummel empirical formulae) and experimentally using 204Tl and 90Sr-90Y radio-isotopes for films at different filler levels 0, 5, 15, 25, 35 and 50 weight percent (Wt.%). In comparison with Thummel empirical formula, the values obtained from Baltakmen's empirical formula is in good agreement with the experiment. The percentage decrease of half value layer values were (52 ± 8) and (60 ± 10)% for 204Tl and 90Sr-90Y, on comparing the values for 0 and 50 Wt.% films, and so the prepared composite films shield the beta particles effectively. The PC that used to shield the low-energy beta particles of 90Sr-90Y can also moderate the higher energy beta particles; the plot of end point energy of 90Sr-90Y versus thickness of PC exhibits a decreasing trend, which confirms that PC acts as an electron moderator.

Characterization and optimization of a ß detector for 18F radio-guided surgery.

Radio-Guided Surgery (RGS) is a nuclear medicine technique to support the surgeon during surgery towards a complete tumor resection. It is based on intraoperative detection of radiation emitted by a radio-pharmaceutical that bounds selectively to tumoral cells. In the past years, an approach that exploits ß- emitting radiotracers has been pursued to overtake some limitations of the traditional RGS based on γ emission. A particle detector dedicated to this application, demonstrating very high efficiency to ß- particles and remarkable transparency to photons, has been thus developed. As a by-product, its characteristics suggested the possibility to utilize it with ß+ emitting sources, more commonly in use in nuclear medicine. In this paper, performances of such detector on 18F liquid sources are estimated by means of Monte Carlo simulations (MC) and laboratory measurements. The experimental setup with a 18F saline solution comprised a "positron signal" spot (a 7 × 10 mm cylinder representing the tumor residual), and a surrounding "far background" volume, that represented for the detector an almost isotropic source of annihilation photons. Experimental results show good agreement with MC predictions, thus confirming the expected performances of the detector with 18F, and the validity of the developed MC simulation as a tool to predict the gamma background determined by a diffuse source of annihilation photons.

Cytogenetic effects of ß-particles in Allium cepa cells used as a biological indicator for radiation damages.

Analysis of cytogenetics effects of ionizing radiation for flora and fauna is essential to determine the impact on these communities and may produce an efficient warning system to avoid harm to human health. Onion (Allium cepa) is a well-established in vivo standard model, and it is widely used in cytogenetics studies for different environmental pollutants. In this work, onion roots were exposed to 0.04-1.44 Gy of ß-particles from a 90Sr/90Y source. We investigated the capacity of brief external exposures to ß-particles on inducing cytogenetic damages in root meristematic cells of onion aiming to verify if onion can be used as a radiation-sensitive cytogenetic bioindicator. A nonlinear increase in the frequencies of chromosomal aberrations and cells with micronuclei was observed. Onion roots exposed to doses 0.13 Gy or higher of ß-particles showed a significant difference (p<0.05) in these frequencies when compared to the unirradiated group. The frequencies of these endpoints showed to be suitable to assess the difference in the dose of beta radiation received from 0.36 Gy. Our research shows the potential of using cytogenetic effects in Allium cepa cells as a biological indicator for a first screening of genotoxic damages induced by brief external exposures to ß-particles.

Simulation study of a simultaneous beta-gamma-ray detection using a 3-layer phoswich detector and Monte Carlo methods.

Combination of two or three dissimilar scintillator materials as a radiation detector has found major role in environmental radiation monitoring. In this paper, a three-layer Phoswich detector including BC-400, YAG, and CsI was designed to efficiently discriminate gamma-ray in the beta events up to 3.2 MeV using a simple rise-time discrimination method. MCNPX Monte Carlo code was used to obtain interaction probability of beta and gamma-rays as well as optimum thicknesses of the layers in the designing process. The optical transport of the system was simulated by GEANT4. In this regard, the pulses from simultaneous beta-gamma emitter sources were detected and discriminated based on pulse's rise-time so that the minimum number of gamma-ray contaminating events was observed in the beta spectrum. The results showed that using the proposed configuration and the method, output pulses with a rise-time shorter than 9 ns have been successfully detected as a beta particle while those with rising time longer than 15 ns have been identified as gamma-ray events. Overall results revealed that using the proposed system, an individual spectrum of beta particles or gamma-rays can be recorded from a simultaneous beta-gamma emitter source that minimizes contribution of the other radiation.

Damages of DNA in tritiated water.

Tritium is a radioisotope of hydrogen emitting low energy ß-rays in disintegration to 3He. DNA molecules are damaged mainly by ß-ray irradiation, and additional damages can be induced by break of chemical bond by nuclear transmutation to inert 3He. Deep knowledges of the mechanisms underlying DNA damages lead to better understanding of biological effects of tritium. This chapter reviews recent experimental and computer simulation activities on quantitative evaluation of damage rates by ß-ray irradiation and nuclear transmutation. The rate of DNA double-strand breaks in tritiated water has been examined using a single molecule observation method. The effects of ß-ray irradiation were not noticeable at the level of tritium concentration of ∼kBq/cm3, while the irradiation effects were clear at tritium concentrations of ∼MBq/cm3. The factors affecting on the DSB rate are discussed. A new image processing method for the automatic measurement of DNA length using OpenCV and deep learning is also introduced. The effects of tritium transmutation on hydrogen bonds acting between the two main strands of DNA have been examined using molecular dynamics simulations. The study showed that the collapsing of DNA structure by the transmutation can be quantitatively evaluated using the root mean square deviation of atomic positions.

Thermoluminescence analysis of beta particle irradiated Gd1-xEuxAlO3 phosphors.

The suitable choice of an activator and host combination is essential for synthesizing very sensitive thermoluminescence phosphors. In addition, conspicuous synthesis variables must be optimized to achieve the maximal response. The research presented herein shows that the most recommendable conditions to improve the thermoluminescence response of beta irradiated Gd1-xEuxAlO3 phosphors were: x = 0.02 for europium stoichiometry and 1500 °C for the calcination temperature. The glow curve recorded for the most sensitive phosphor was partially erased by photo-bleaching, and thus, should yield optically stimulated luminescence.

DOSE AND DOSE-RATE DEPENDENCE OF DSB-TYPE MUTANTS INDUCED BY X-RAYS OR TRITIUM BETA-RAYS: AN APPROACH USING A HYPERSENSITIVE SYSTEM.

To evaluate biological effects triggered by low levels of radiation, we established a uniquely sensitive experimental system to detect somatic mutations. By using the system, we found that mutant frequencies induced by X-rays were statistically significant at doses over 0.15 Gy, and a linear dose relationship with the mutant frequency was observed at doses over 0.15 Gy. The mutation spectra analysis revealed that mutation events generated by X-ray doses below 0.1 Gy were similar to those observed in unirradiated controls. In addition, a significant inflection point for both, the mutant frequency and the mutation spectra, was found at dose-rates around 11 mGy/day when cells were cultured in medium containing tritiated water. Because induced radiation-type events presented a clear dose/dose-rate dependency above the critical dose or the inflection point, these observations suggest that mutation events generated by radiation could change at a threshold dose-rate or a critical dose.

PERFORMANCE EVALUATION OF COMMERCIAL SCINTILLATION COCKTAILS FOR LOW-LEVEL TRITIUM COUNTING BY HIGH-CAPACITY LIQUID SCINTILLATION COUNTER.

Low-background liquid scintillation counter is one of the popular measuring instruments used to investigate tritium radioactivity in environmental media. These instruments require the liquid sample and organic solvent to be mixed for tritium measurement. In the European Union, the registration, evaluation, authorization and restriction of chemicals regulation was established to control the use of chemical substances of very high concern. It is important to find continuously available alternative reagents. In this paper, a performance evaluation was conducted using four scintillation cocktails according to Japanese conventional procedure; although one of them, Gold Star LT2, contains nonylphenol ethoxylate, it will continue to be available for research and development. From the evaluation results it was confirmed that Gold Star LT2 would be a satisfactory alternative scintillator, which is similar performance of Ultima Gold LLT.

Microdistribution of internal radiation dose in biological tissues exposed to 56Mn dioxide microparticles.

Manganese-56 (56Mn) was one of the dominant neutron-activated radionuclides during the first hours following the atomic-bombing of Hiroshima and Nagasaki. The radiation spectrum of 56Mn and the radiation emission from excited levels of 56Fe following 56Mn beta-decay include gamma-quanta, beta-particles, Auger electrons and X-rays. The dispersion of neutron activated 56Mn in the air can lead to entering of radioactive microparticles into the lungs. The investigation of spatial microdistribution of an internal dose in biological tissue exposed to 56Mn is an important matter with regards to the possible elevated irradiation of the lung alveoli and alveolar ducts. The Monte Carlo code (MCNP-4C) was used for the calculation of absorbed doses in biological tissue around 56Mn dioxide microparticles. The estimated absorbed dose has a very essential gradient in the epithelium cells of lung alveoli and alveolar duct: from 61 mGy/decay on the surface of simple squamous cells of epithelium to 0.15 mGy/decay at distance of 0.3 µm, which is maximal cell thickness. It has been concluded that epithelial cells of these pulmonary microstructures are selectively irradiated by low-energy electrons: short-range component of beta-particles spectrum and Auger electrons. The data obtained are important for the interpretation of biological experiments implementing dispersed neutron-activated 56Mn dioxide powder.

External dose estimates of laboratory rats and mice during exposure to dispersed neutron-activated 56Mn powder.

Estimates of external absorbed dose in experimental animals exposed to sprayed neutron-activated 56Mn powder are necessary for comparison with internal absorbed doses estimated under the same exposure conditions, which is required for a correct interpretation of the observed biological effects. It has been established that the measured dose of external absorbed dose as a result of gamma irradiation range 1-15 mGy, which is order of magnitude less than the maximal dose of internal gamma and beta irradiation of the whole body of the same experimental animals irradiated under the same conditions: according to the available literature data, the maximal values ​​of absorbed dose of internal gamma-beta irradiation of the whole body are in the range of 330 mGy-1200 mGy for mice and 100 mGy-150 mGy for rats. It is concluded that under the conditions of experiments with dispersed neutron-activated powder 56MnO2, internal gamma-beta irradiation of experimental animals is the main factor of radiation exposure compared to external gamma irradiation.

Pathological observation of the effects of exposure to radioactive microparticles on experimental animals.

Internal radiation exposure from neutron-induced radioisotopes that were environmentally activated following an atomic bombing or nuclear accident should be considered for a complete picture of the pathologic effects on survivors. Inhaled hot particles expose neighboring tissues to very high doses of particle beams, which can cause local tissue damage. Experimentally, a few µm of 55MnO2 powder was irradiated with neutrons at a nuclear reactor in order to generate 56MnO2 that emits ß-rays. Rats were irradiated via inhalation. Pathological changes in various rat tissues were examined. In addition, the 56Mn ß energy spectrum around the particles was calculated to determine the local dose rate and the cumulative dose. This review focuses on our latest pathological findings in lungs with internal radiation injury and discusses the pathological changes of early event damage caused by localized, very high-dose internal radiation exposure, including apoptosis, elastin stigma, emphysema, hemorrhage and severe inflammation. The pathological findings of lung tissue due to internal radiation exposure of 0.1 Gy were severe, with no pathological changes observed due to external exposure to γ radiation at a dose of 2.0 Gy. Therefore, it is suggested that new pathological analysis methods for internal exposure due to radioactive microparticles are required.

Radiopharmaceutical Treatments for Cancer Therapy, Radionuclides Characteristics, Applications, and Challenges.

Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been intensified on the development of radionuclides and their application in radiopharmaceuticals (RPS) which will certainly influence and expand therapeutic approaches in the future treatment of patients. Alpha or beta particles and Auger electrons are used for therapy purposes, and each has advantages and disadvantages. The radionuclides labeled drug delivery system will deliver the particles to the specific targeting cell. Different radioligands can be chosen to uniquely target molecular receptors or intracellular components, making them suitable for personal patient-tailored therapy in modern cancer therapy management. Advances in nanotechnology have enabled nanoparticle drug delivery systems that can allow for specific multivalent attachment of targeted molecules of antibodies, peptides, or ligands to the surface of nanoparticles for therapy and imaging purposes. This review presents fundamental radionuclide properties with particular reference to tumor biology and receptor characteristic of radiopharmaceutical targeted therapy development.

Evaluating the intensity of the 'prompt' 140.5 keV γ-ray of 99Mo using a 4παß(LS)-γ(HPGe) measurement system.

The absolute intensity for the 'prompt' 140.5 keV gamma-ray of 99Mo was evaluated using the ß-γ coincidence technique. A liquid sample of 99Mo was prepared from a99Mo/99mTc generator and measured in a 4παß(LS)-γ(HPGe) system that comprises a Liquid Scintillator (LS) detector and a High-Purity Germanium (HPGe) detector. The sample was introduced into scintillation fluid embedded in a photo-reflector assembly that provides almost 100% efficiency for detecting ß particles (in the energy range of intreset). The combination of the HPGe and the LS detectors provided a highly effective rejection mechanism for non-coincident events. Thereby, the distinction between the detected 140.5 keV events originating from decays of 99mTc (IT) and those from transitions bypassing the metastable state could be obtained and the 'prompt' intensity was evaluated directly. The system was calibrated for detecting ß particles and γ-rays using radioactive sources of known activities and having identical geometry as the sample containing 99Mo. The absolute intensity of the 'prompt' 140.5 keV was found to be (5.21 ± 0.02stat±0.16sys)%, in good agreement with results from more recently reported works.

Simultaneous determination of gross alpha/beta activities in water by liquid scintillation counting and its applications in the environmental monitoring.

Based on the standards of ISO11704-2018 and ASTM D7283-17, a method for simultaneous determination of gross alpha and gross beta activity concentrations in water by liquid scintillation counting (LSC) was established, which can be applied to various types of water samples in routine monitoring, such as drinking water, groundwater, geothermal water, seawater, and radioactive wastewater. The sample's pH value and concentrated volume must be controlled to avoid quenching as much as possible. The validation tests show that the deviations of gross alpha and gross beta activities can satisfy quality control requirements in a wide range of activity ratios from 1:102 to 67:1. For the actual samples, the measurement results of the LSC method are in good agreement with those of the thick source method, in which the relative deviations of gross alpha and gross beta are both less than 15% for these two methods. Moreover, the LSC method performs better in detection limit and has a simpler pretreatment process than the thick source method.

Effect of electrode separation and electrode backscatter thickness of a parallel plate ionization chamber on the measurement of dose to tissue in beta radiation fields.

Plane parallel plate ionization chamber (PPC) is used in dosimetry especially for beta particles and low energy electron beam. The response of the PPC is affected by the electrode separation, thickness and material of backscatterer. The effect of electrode separation arises due to the well-known inscattering effect of electron which causes fluence perturbation inside the chamber cavity. The perturbation is caused due to reduced electron scattering in the chamber cavity compared to an ideal phantom material and it depends on the thickness of the cavity. Furthermore, the response of PPC also gets affected by the material behind the air cavity. Variation in the response depends on the thickness and the atomic number of the material behind collecting electrode of the PPC. The theoretical studies on the effect of collecting electrode backscatter thickness and electrode separation on the response of a PPC used as a transfer standard in ISO 6980 reference beta radiation field from 85Kr, 90Sr-90Y and 106Ru-106Rh radionuclides are presented. Multi-particle transport code FLUKA is used for the studies. The Polymethyl Methacrylate (PMMA) plate having 3.5 mm thickness is found to provide full backscatter for the above beta radionuclides. It is also observed that even for a well-guarded PPC, as the chamber electrode separation increases, the measured depth dose curve deviates from the ideal depth dose curve and the effective point of measurement (EPOM) of the PPC shifts towards downward direction from chamber reference point. It is also observed that the deviation between ideal and measured depth dose curve (related to EPOM shift) depends on the cavity thickness of the PPC. In the present work, optimization of design parameters of a PPC is carried out to establish it as a transfer standard in compliance with ISO 6980 for the standardization of reference beta radiation fields from 85Kr, 90Sr-90Y and 106Ru-106Rh radionuclide.

[Dominant Research Contribution of Dr. Eiichi Tanaka in the Field of Very Weak Radioactivity Measurements].

This article gives dominant research contributions of the late Dr. Eiichi Tanaka in the field of very weak radioactivity measurements with a new type of an extremely low background ß-ray scintillation spectrometer, which consists of a large plastic scintillator and a gas-flow GM counter located in the small hollow in the bottom part of the plastic scintillator. The pulse signals from plastic scintillator are coincidence-gated by the pulses from the GM counter. Dominant background signals due to the energetic muons still appear in the higher region than 3.5 MeV even with coincidence gating mode, but extreme reduction of background can be attained in the 0～3 MeV region which is essentially important in the ß-ray spectrometry for most of radionuclides.

The ultra high sensitivity blood counter: a compact, MRI-compatible, radioactivity counter for pharmacokinetic studies inµl volumes.

Quantification of physiological parameters in preclinical pharmacokinetic studies based on nuclear imaging requires the monitoring of arterial radioactivity over time, known as the arterial input function (AIF). Continuous derivation of the AIF in rodent models is very challenging because of the limited blood volume available for sampling. To address this challenge, an Ultra High Sensitivity Blood Counter (UHS-BC) was developed. The device detects beta particles in real-time using silicon photodiodes, custom low-noise electronics, and 3D-printed plastic cartridges to hold standard catheters. Two prototypes were built and characterized in two facilities. Sensitivities up to 39% for18F and 58% for11C-based positron emission tomography (PET) tracers were demonstrated.99mTc and125I based Single Photon Emission Computed Tomography (SPECT) tracers were detected with greater than 3% and 10% sensitivity, respectively, opening new applications in nuclear imaging and fundamental biology research. Measured energy spectra show all relevant peaks down to a minimum detectable energy of 20 keV. The UHS-BC was shown to be highly reliable, robust towards parasitic background radiation and electromagnetic interference in the PET or MRI environment. The UHS-BC provides reproducible results under various experimental conditions and was demonstrated to be stable over days of continuous operation. Animal experiments showed that the UHS-BC performs accurate AIF measurements using low detection volumes suitable for small animal models in PET, SPECT and PET/MRI investigations. This tool will help to reduce the time and number of animals required for pharmacokinetic studies, thus increasing the throughput of new drug development.

Ligand Engineering of Titanium-Oxo Nanoclusters for Cerenkov Radiation-Reinforced Photo/Chemodynamic Tumor Therapy.

The therapeutic effect of general photodynamic therapy (PDT) is gravely limited by the poor penetration depth of exogenous light radiation. In recent years, Cerenkov radiation (CR) has been exploringly applied to overcome this critical defect. However, the currently reported type I photosensitizers for CR-induced PDT (CRIT) are only TiO2 nanoparticle-based agents with numerous fatally intrinsic drawbacks. Herein, we developed NH2-Ti32O16 nanocluster (NTOC)-derived ultrasmall nanophotosensitizers (NPSs, denoted as TDPs) via innovate ligand engineering. The introduced dopamine (DA) ligands not only facilitate the water solubility and photocatalytic properties of NPSs but also involve the tumor-targeting behavior through the binding affinity with DA receptors on cancer cells. Under CR irradiation, TDPs enable efficient hydroxyl radical (·OH) generation benefiting from the enhanced separation of hole (h+)-electron (e-) pairs, where the h+ will react with H2O to execute type I PDT and the transferred e- can realize the augmentation of Ti3+ to substantially promote the therapeutic index of chemodynamic therapy. This study provides an easy but feasible strategy for constructing versatile NPSs with an ultrasmall framework structure, propounding a refreshing paradigm for implementing efficient CR-induced combined therapy (CRICT) and spurring the development of CR and titanium-familial nanoplatforms in the fields of photocatalysis and nanocatalytic medicine.