Helicobacter pylori (H. pylori) infection remains a significant global health challenge, contributing to various gastrointestinal disorders, including peptic ulcers and gastric cancer. The bacterium's urease enzyme plays a pivotal role in its survival by neutralizing gastric acidity, making urease inhibitors a promising therapeutic strategy. This study explores the green synthesis of silver nanoparticles (AgNPs) using Persian lime (Citrus latifolia T.) fruit extract as a reducing and stabilizing agent, optimized via the Taguchi method to achieve minimal particle size for enhanced bioactivity. Characterization techniques such as Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and UV-Vis spectroscopy confirmed the formation of spherical AgNPs with an average size of 27.63 nm and a zeta potential of -13.8 mV, indicating good stability. The green synthesized AgNPs exhibited potent urease inhibitory activity, with an IC50 value of 15.02 ± 2.36 µg/mL, surpassing that of Persian lime (Citrus latifolia) fruit extract (IC50= 33.31 ± 1.43 µg/mL). In contrast, chemically synthesized AgNPs counterparts exhibited minimal inhibitory activity against urease. These findings highlight the potential of green synthesized AgNPs as effective urease inhibitors with possible relevance to H. pylori-associated pathogenesis. Since H. pylori urease is structurally homologous to the jack bean urease used in this study, these results warrant further investigation using direct anti-H. pylori assays and in vivo models. The integration of natural extracts in nanotechnology not only reduces environmental impact but also enhances biocompatibility, paving the way for novel antimicrobial therapies. Consistently refer to Sample 7 conditions (pH 5, 3500 µL, 5 mM, 80 °C) as the experimentally validated optimum, while noting the Taguchi-predicted conditions where appropriate.

Cancer remains to be a major life-threatening illness, prompting ongoing efforts to develop innovative treatment methods. Nanotechnology presents distinct advantages by enabling targeted delivery to malignant cells while minimizing damage to surrounding healthy tissue. Quantum dots (QDs), nanoscale semiconductor particles, have emerged as promising tools for tumor imaging, diagnosis, prevention and treatment. Nonetheless, their application in biomedicine faces challenges due to cytotoxicity, which may affect normal cells and red blood cells (RBCs). To mitigate these issues, green synthesis utilizing plant extracts offers an environmentally friendly and cost-effective method to enhance biocompatibility. This study investigated the synthesis of cadmium sulfide (CdS) QDs, which were subsequently coated with ethanolic extracts from Heracleum persicum (HP) and Quercus infectoria (QI). The successful synthesis and surface modifications were verified through various techniques, including ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), and scanning electron microscopy (SEM). DLS results indicated hydrodynamic sizes of 258 nm for CdS@HP and 253 nm for CdS@QI, with zeta potential values shifting from - 22.4 mV for bare CdS to - 25.0 mV for CdS@HP and - 23.9 mV for CdS@QI, suggesting enhanced colloidal stability. Biological assessments, incorporating 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and hemolysis assays, revealed that bare CdS QDs exhibited substantial cytotoxicity and hemolytic activity. The HP-coated QDs achieved the highest cell viability and the lowest hemolysis, whereas the QI-coated QDs showed moderate protective effects but a slightly increased hemolytic response. These findings highlight the potential of plant-based coatings to improve the safety and stability of CdS QDs for future biomedical applications.

Bimetallic nanoparticles have emerged as promising radiosensitizers for improving the efficacy of cancer radiotherapy by enhancing local radiation energy deposition while maintaining acceptable biocompatibility. In this study, we developed and evaluated a novel Ag–Bi₂S₃@BSA bimetallic nanoplatform using an integrated experimental–computational approach combining in vitro biological evaluation with Monte Carlo (MCNPX) simulation. Ag–Bi₂S₃ nanoparticles were synthesized and coated with bovine serum albumin (BSA) to improve colloidal stability and biocompatibility. Their physicochemical properties were characterized using Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), dynamic light scattering (DLS), ultraviolet–visible (UV–Vis) spectroscopy, and X-ray diffraction (XRD). Radiosensitizing efficacy was evaluated in 4T1 breast cancer cells using the MTT assay following irradiation with a 6 MV X-ray beam. In parallel, Monte Carlo simulations were performed to quantify the physical dose enhancement factor (DEF) at different nanoparticle concentrations. The Ag–Bi₂S₃@BSA nanoparticles enhanced radiation-induced cytotoxicity in a concentration-dependent manner, with the lowest cell viability (10.2%) observed at 600 µg/mL under 6 Gy irradiation. Consistently, the Monte Carlo simulations predicted the highest physical DEF at the same nanoparticle concentration. Although the simulated DEF represents physical dose enhancement rather than biological radiosensitization, the agreement between the computationally predicted optimal concentration and the experimental findings supports the value of integrating computational dosimetry with biological validation during nanoparticle optimization. These results identify Ag–Bi₂S₃@BSA as a promising bimetallic radiosensitizer for preclinical investigation and provide a rational framework for the future development and evaluation of multifunctional nanoparticle-assisted radiotherapy.

This study reports the synthesis, comprehensive characterization, and biological evaluation of quercetin-encapsulated bismuth oxide nanoparticles (Bi2O3@Quercetin) as a novel theranostic platform for combined chemo-radiotherapy of breast cancer. Bi2O3 nanoparticles were prepared via a solvothermal route and loaded with quercetin through a simple adsorption process, achieving a drug loading efficiency of 27.5 ± 1.8% and a theoretical maximum loading capacity of 34.76% (computational prediction). The synthesized Bi2​O3​@Quercetin nanocomposite exhibited a spherical morphology with an average dry core size of 64 nm (as determined by electron microscopy), a hydrodynamic diameter of approximately 240 nm (via dynamic light scattering), and a stable negative zeta potential of −18.1 mV, ensuring excellent colloidal stability. XRD confirmed the monoclinic α-Bi2O3 phase, while FT-IR and UV-Vis analyses verified successful quercetin encapsulation. In vitro cytotoxicity assays on the 4T1 murine breast cancer cell line demonstrated significantly higher anticancer activity of Bi2O3@Quercetin compared to free quercetin, both alone and in combination with 4 Gy X-ray irradiation, owing to enhanced cellular uptake and synergistic ROS generation. Hemolysis studies confirmed excellent blood compatibility (<5% at 160 μg/mL). pH-responsive release studies revealed sustained quercetin release at physiological pH (60% after 130 h) and accelerated release in acidic tumor microenvironment (92% at pH 5.7), ideal for targeted delivery. Extensive computational investigations (DFT, molecular docking, and 10-ns MD simulations) elucidated the molecular basis of high loading capacity, strong non-covalent interactions (binding energies up to −49.74 kcal/mol), reduced HOMO–LUMO gap (1.17 eV), and excellent structural stability of the fully loaded nanosystem. These findings establish Bi2O3@Quercetin as a promising, biocompatible candidate for further evaluation as a radiosensitizing nanocarrier, demonstrating encouraging in vitro therapeutic efficacy for combined chemo-radiotherapy applications.

In this study, copper oxide nanoparticles (CuO-NPs) were synthesized using a green, eco-friendly method employing the ethanolic extract of Calendula officinalis. The synthesis leveraged the plant's rich phytochemical profile to act as both reducing and capping agents, resulting in nanoparticles with enhanced biocompatibility and stability. The CuO-NPs were characterized using UV-Vis spectroscopy, FT-IR, X-ray diffraction (XRD), dynamic light scattering (DLS), and Atomic Force Microscopy (AFM), confirming their formation, functional groups, crystalline structure, and nanoscale dimensions. The average particle size was ~ 6.66 nm, with a negative zeta potential indicating good colloidal stability. Hemocompatibility and cytotoxicity were evaluated via hemolysis and MTT assays on normal HFF-2 human fibroblast cells. Results showed less than 5% hemolysis and relatively low cytotoxicity compared to chemically synthesized counterparts, highlighting the safety of the green synthesis method. This study demonstrates the potential of-mediated CuO-NPs as promising candidates for biomedical applications Calendula officinalis such as drug delivery and cancer therapy.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, oxidative stress, and neuroinflammation. Betanin, a natural antioxidant, has shown neuroprotective potential, but its clinical use is limited by poor bioavailability. This study investigates the effects of betanin-loaded nanomicelles, designed to enhance brain delivery, in a scopolamine-induced rat model of AD. Nanomicelles were synthesized and characterized using TEM, DLS, and FT-IR. Rats received either pre- or post-treatment with betanin nanomicelles, free betanin, donepezil, or saline. Cognitive performance was assessed using the Morris Water Maze. Gene expression levels of AQP4, BDNF, SIRT6, and Seladin-1 were measured using real-time PCR, and antioxidant activity was evaluated by assessing glutathione (GSH) and glutathione reductase (GR) in hippocampal tissue. Betanin nanomicelles improved spatial memory, increased BDNF and SIRT6 expression, and reduced AQP4 levels, indicating potential neuroprotection. Seladin-1 expression was notably elevated in the pre-treatment group, suggesting support for neuronal survival. Antioxidant assays showed restoration of GSH and GR activity. These findings suggest that betanin nanomicelles may enhance cognitive function and modulate neuroprotective pathways more effectively than free betanin, supporting their potential as a novel therapeutic strategy for AD.

The widespread presence of ciprofloxacin (CIP) in aquatic environments poses significant risks to public health and ecosystems due to its role in promoting antibiotic resistance. Addressing this challenge, we developed graphene oxide-like carbon nanosheets (CNSs) from onion peel waste as a low-cost and sustainable adsorbent for efficient CIP removal from water, where the cost savings originate from free raw materials and an energy-efficient synthesis, thereby valorizing waste and reducing pollutants as key sustainability indicators. The CNSs, synthesized via pyrolysis and ultrasonic exfoliation, exhibited abundant oxygen-containing functional groups and a negatively charged surface (zeta potential: -20.9 mV), with TEM confirming nanosheet structure. Under optimized conditions (pH 7, 0.4 g L-1 adsorbent dosage), the CNSs achieved 90% CIP removal (qmax= 51.28 mg g-1), with adsorption following pseudo-second-order kinetics and the Freundlich isotherm. Reusability tests showed 50% efficiency retention after five cycles. Thermodynamic analysis confirmed the process was spontaneous and exothermic (ΔG° = -7.19 to -6.38 kJ mol-1, ΔH° = -15.26 kJ mol-1). Density functional theory calculations revealed hydrogen bonding between CIP’s amine groups and CNS hydroxyls as the primary adsorption mechanism, with strong binding energies (-87.0 kJ mol-1). This work highlights the potential of agricultural waste-derived nanomaterials as eco-friendly and high-performance solutions for pharmaceutical wastewater remediation, offering a dual benefit of waste valorization and environmental protection.

Due to their special features, quantum dots have recently attracted the attention of researchers in the fields of imaging, drug delivery, and cancer treatment. In this study, we prepared Ag2S quantum dots (QDs) intending to control the nucleus growth and reduce toxicity in Artemisia dracunculus (tarragon) extract substrate using the green synthesis method. Synthesized nanoparticles were analyzed using different characterization techniques. The DLS data analysis showed that Ag2S QDs prepared by the green synthesis method have a mean size of 56 nm, which is smaller compared to chemical synthesis. Additionally, the synthesis of Ag2S QDs with tarragon extract decreased the zeta potential from − 13 eV to -21 eV, which can be effective in enhancing colloidal stability and increasing their presence in the bloodstream. Examining the hemolysis data showed that the synthesis of Ag2S QDs with tarragon extract significantly reduces the lysis of red blood cells by modifying the surface chemistry. The cell culture data also confirmed the results of hemolysis, indicating increased cell viability with Ag2S QDs tarragon. These results indicated that the use of tarragon extract as a green synthesis material contributes to the biocompatibility and safety of Ag2S QDs.

Radiotherapy (RT) is one of the main methods of breast cancer treatment that can be used alone or together with other therapy methods. Also, photothermal therapy (PTT) has attracted attention as another modality in tumor treatment. Recently, combination therapy has been proposed as a new alternative approach to increase the effectiveness of cancer therapy. On the other side, the investigations on the use of metal-based hybrid nanoparticles (MHNs) simultaneously as a radiosensitizer and a photothermal agent in the case of combination of RT and PTT have been increased to enhance the efficiency of cancer treatment too. In this research, Bi2S3 NPs, gold nanorods (GNRs) and their hybrid (GNRs-Bi2S3 as new MHNs) were synthesized. Then, the quality control tests were confirmed the successful synthesis of NPs and GNRs-Bi2S3 hybrid. Next, the likely enhanced effect of combination of RT (at two X-ray doses of 2 and 6 Gy) and PTT (at 808 nm wavelength with 1500 mW power) using of Bi2S3-GNRs hybrid (at 3 concentrations of 50, 100 and 200 µg/ml) was investigated for breast cancer therapy in comparison with alone Bi2S3 NPs or GNRs in single therapy of RT or PTT. The cell viability test showed a significant reduction at all tested concentrations of Bi2S3-GNRs hybrid after single therapy method of RT or PTT. The synthesized hybrid was even more effective in case of combination therapy method compared to use of each of modalities or NPs alone especially at concentration of 200 µg/ml and X-ray dose of 6 Gy. In summary, our novel hybrid showed enhanced effectiveness in killing of breast cancerous cells as MHNs in combination therapy method of RT and PTT.

AIMS:The development of multifunctional nanoplatforms capable of simultaneous therapeutic and diagnostic applications is a growing focus in biomedical research. METHODS/MATERIALS:In this study, silver sulfide - silver nanoparticles coated with bovine serum albumin (Ag₂S-Ag@BSA) were synthesized via a one-step biomineralization method at room temperature. Methotrexate (MTX), a chemotherapeutic agent, was chemically conjugated to the nanoparticles to enhance targeted anticancer activity. Comprehensive characterization using FTIR, UV-Vis, XRD, TEM, and DLS confirmed successful synthesis. RESULTS:TEM analysis revealed spherical nanoparticles with an average diameter of 12.02 nm, while DLS indicated a hydrodynamic size of 40 nm, a polydispersity index of 0.20, and a zeta potential of -24 mV, reflecting good stability. Drug release studies demonstrated enzyme-responsive behavior, with significantly increased MTX release in the presence of proteinase K, simulating intracellular protease activity. In vitro and in vivo assessments revealed that the combined treatment strategy - including MTX delivery, X-ray exposure, and radiosensitization - achieved superior therapeutic outcomes compared to monotherapies. Histopathological analysis confirmed the biocompatibility of the nanoplatform, with no observable tissue damage. Furthermore, the nanoparticles exhibited potential as computed tomography (CT) contrast agents. CONCLUSION:These results suggest that Ag₂S-Ag@BSA-MTX nanoparticles offer a promising multifunctional approach for cancer theranostics.

This study details the design, synthesis, and validation of the novel MnO₂-Au-BSA@CUR construct, utilizing a tightly integrated computational (Docking, DFT, MD) and experimental approach to understand its structure and function, and demonstrating significant in vitro synergistic radiosensitization as a key outcome for potential breast cancer therapy. The nanoparticles, comprising manganese dioxide (MnO2) for oxygen generation, gold (Au) for radiosensitization, bovine serum albumin (BSA) for biocompatibility, and curcumin (CUR) for dual chemotherapeutic and radioprotective effects, were synthesized and characterized using techniques such as UV-Vis spectroscopy, XRD, FTIR, and TEM, confirming their uniform morphology and successful conjugation. As shown in the TEM image, the average size of MnO2-Au-BSA@CUR nanoparticles is about 39.25 nm, with a spherical shape. DLS results show the hydrodynamic size of MnO2-Au-BSA@CUR nanoparticles with a Z-average of 190 nm with polydispersity index (PdI) of nanoparticles to be 0.391 and zeta potential of nanoparticles is -24.7 mV. In vitro studies on 4T1 breast carcinoma cells demonstrated dose-dependent cytotoxicity and enhanced radiosensitization under 4 Gy X-ray irradiation, attributed to Au's increased X-ray absorption and CUR's synergistic action. The pH-dependent release of CUR, significantly enhanced under acidic conditions, represents a key design feature for promoting tumor-specific delivery and minimizing systemic exposure. Computational analyses, including molecular docking, density functional theory (DFT), and molecular dynamics (MD) simulations, elucidated the nanoplatform's stability and interactions, revealing strong binding energies (-89.23 kcal/mol for CUR with α-MnO₂-Au (111)) and a narrow HOMO-LUMO gap (2.05 eV) that supports efficient charge transfer for radiosensitization. This study establishes the MnO2-Au-BSA@CUR nanoplatform as a promising theranostic agent, integrating experimental and computational insights to advance multifunctional nanomedicine for cancer therapy.

Lung cancer was associated with a high mortality rate. However, the critical challenges in radiotherapy are enhancing tumor damage and minimize the side effects to the healthy tissues. A strategic approach to overcome this challenge includes using different radiosensitizer to increase the efficiency of radiotherapy while reducing side effects on normal tissues. Significant progress has been achieved in the development of materials based on nanotechnology. Nanomaterial-based radiosensitizers increase the tumor cells sensitivity to ionizing radiation, and accelerating DNA damage through the production of free radicals. Therefore, in the present study, the radio sensitization efficiency of silver nanoparticles-loaded niosomes for the treatment of lung cancer has been investigated. Silver nanoparticles synthesis protocol was based on the chemical reduction method and then they were loaded inside niosomes using the thin layer hydration method. The physical and chemical characteristics of the designed nanosystems were evaluated using different instrumental and laboratory methods, including FT-IR, UV-Vis, DLS, FE-SEM, EDAX techniques. To investigate the cytotoxicity of prepared nanosystems, the MTT assay was used against two cell lines, including normal human lung cells (MRC-5) and lung cancer cells (A549), in the absence and presence of radiotherapy rays. The size and poly dispersity index of the resulting nanoparticles are in the range of Nano scale and are suitable for cancer studies. The morphology of the resulting nanoparticles was found to be spherical and homogeneous. The structural and optical analysis of the nanoparticles showed the successful synthesis of niosomes containing silver nanoparticles. Also, the EDAX technique confirmed the presence of silver nanoparticles inside niosomal formulations. The encapsulation efficiency of silver nanoparticles was 49.9% ± 0.40 for silver nanoparticles. In the following, the biocompatibility of the formulation prepared using the MTT method toward the normal cell line MRC-5 showed that no significant toxicity in the studied concentrations. MTT test toward the A549 lung cancer cell line showed an increase in the toxicity of radiotherapy in lung cancer. Our study showed that silver nanoparticles-loaded niosomal nanosystems possess significant therapeutic efficacy radiotherapy of the lung cancer. On the other hand, loading silver nanoparticles inside niosomal carriers reduced the toxicity of silver nanoparticles and introduced them as a suitable option for cell experiments. Also, we showed that the synthesized formulations in combination with radiotherapy increase the efficiency treatment through its synergistic effect.

The green synthesis approach for nanoparticle production offers several advantages over traditional physical and chemical methods. Notably, it avoids the use of hazardous chemicals and acts as a cost-effective and eco-friendly process. This study focuses on the green synthesis of zinc oxide nanoparticles (ZnO- NPs) using the Punica granatum fruit peel extract. Punica granatum fruit peel extract was chosen for the environmentally friendly synthesis of ZnO nanoparticles due to its rich composition of bioactive compounds, including polyphenols, flavonoids, and tannins, which function as natural reducing and stabilizing agents. The morphological, structural, and optical observations were confirmed through various techniques such as X- ray diffraction (XRD), UV-Vis spectroscopy, field emission scanning electron microscopy (FE- SEM), Fourier- transform infrared spectroscopy (FT- IR), EDAX and dynamic light scattering (DLS). To further investigate the impact of synthesized nanoparticles, hemolysis and MTT (3-[4, 5- dimethylthiazol- 2- yl]- 2, 5-diphenyl tetrazolium bromide) assays were conducted. The morphology of the resulting nanoparticles was found to be spherical and homogeneous. DLS results show the hydrodynamic size of nanoparticles with a Z-average of 187 nm with polydispersity index (PdI) of nanoparticles to be 0.298 and zeta potential of nanoparticles is -17.6 mV. The results showed that green synthesis using Punica granatum fruit peel extract resulted in significantly higher cell viability in culture compared to traditional chemical synthesis. This finding highlights the project's aim to emphasize the advantages of the green synthesis approach on HFF-2 cell lines. These results offer powerful evidence for the potential capability of green synthesis ZnO nanoparticles with Punica granatum fruit peel extract opens up a new avenue of research in this area.

Helicobacter pylori (H. pylori), a significant human pathogen, is strongly associated with various gastrointestinal diseases, including gastric adenocarcinoma. While quadruple bismuth therapy remains a primary treatment, increasing antibiotic resistance necessitates the development of alternative, selective, and antibiotic-free antibacterial strategies. Metal-based nanoparticles (NPs), particularly bismuth NPs, have shown promising antibacterial properties. In this study, we investigated the inhibitory effects of bismuth oxide NPs and a bismuth oxide-baicalein nanosystem against H. pylori. Our results demonstrated that bismuth oxide NPs demonstrated 1.5 times greater inhibitory activity (IC50 = 286.2 ± 1.6 µg/mL) than baicalein, while the nanosystem (Bi2O3@baicalein) displayed significant urease inhibition (IC50 = 151.5 ± 1.1 µg/mL), outperforming baicalein by 2.69 times (IC50 = 408.9 ± 1.5 µg/mL). The nanosystem was measured at approximately 254.2 nm with a zeta potential of − 19.3 mV, and baicalein loading was determined to be 20.91

Background: Olive stones, a byproduct of agricultural processes, hold significant potential for sustainable applications. In this study, activated carbon and carbon nanosheets derived from olive stones were utilized as adsorbents for removing methylene blue (MB) dye from aqueous solutions. Methods: The preparation of activated carbon and carbon nanosheets involved grinding olive stones, followed by pyrolysis and ultrasonic treatment. The structural and morphological properties of the adsorbents were characterized using field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) analyses. Batch adsorption experiments were conducted to evaluate the influence of adsorbent dose, pH, initial dye concentration, and temperature on the adsorption process. Results: Under optimized conditions, the removal efficiencies of activated carbon and carbon nanosheets were 63% and 76%, respectively, with corresponding adsorption capacities of 50.6 and 60.9 mg/g. Adsorption isotherms were well described by the Langmuir model for both adsorbents, while kinetic studies revealed conformity to the pseudo-second-order model. Conclusion: The findings confirm that activated carbon and carbon nanosheets derived from olive stones are efficient and cost-effective adsorbents, exhibiting high adsorption capacities for MB and rapid equilibrium times in aqueous solutions.

Quercetin, a bioactive flavonoid with limited bioavailability, was investigated using BSA-coated MnFe 2 O 4 nanoparticles as a novel delivery system.

Breast cancer is the most common and significant threat affecting women globally. Traditional methods have been widely used in cancer treatment for many years. However, the unavoidable side effects of these approaches are undeniable. Nanotechnology Through combination therapy offers the potential to improve traditional cancer treatments by reducing side effects and enhancing efficacy. In this project, we examined the potential of single-walled carbon nanotubes (SWCNTs) as advanced delivery systems for chemotherapy agents directly to tumors, as well as their role as platforms for the development of radiation sensitizers to enhance the efficacy of radiation therapy without drugs and combination therapy with chemotherapy. To confirm the successful formation of the nanoparticles, we conducted various techniques such as Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), UV–visible spectroscopy, and X-ray diffraction (XRD) to ensure accurate verification. To evaluate the cytotoxicity of SWCNTs -Au-CUR nanoparticles, we performed MTT and hemolysis assays. Subsequently, we assessed the effectiveness of the synthesized nanoparticles against cancer cells at different concentrations, with and without the aid of X-ray. Observed results showed the correct creation and high efficacy of these nanoparticles on cancerous cells. It also showed that the presence of X-rays amplified nanoparticle toxicity, increased the ROS levels in the cancerous cells, and resulted in more effective induction of DNA damage.

Synergistic radiochemotherapy for breast cancer is often hindered by critical challenges, including tumor hypoxia and inherent radioresistance, which limit treatment efficacy. Overcoming these barriers requires advanced nanoplatforms capable of modulating the tumor microenvironment while precisely codelivering therapeutics. Here, we address these challenges by designing and developing a multifunctional bovine serum albumin (BSA)-stabilized MnO2-Bi2S3-Methotrexate (MTX) nanoplatform. Synthesized through a biomineralization approach, the nanoplatform exhibits a hydrodynamic diameter of 67 nm and a zeta potential of -20.9 mV, ensuring excellent colloidal stability. Experimental investigations revealed a pH-responsive MTX release profile and enhanced radiosensitization, which is attributed to the high-Z properties of Bi2S3 and the hypoxia-mitigating, oxygen-generating function of MnO2. To gain deeper mechanistic insights, computational analyses were employed: molecular docking studies confirmed MTX's stable binding to BSA subdomains IIA and IIIA with a binding free energy (Delta G) of -14.79 kcal/mol, while density functional theory (DFT) calculations revealed a robust interaction energy of -154 kcal/mol for the MTX-alpha-MnO2-Bi2S3 complex, featuring a HOMO-LUMO gap of 2.56 eV and a Fermi energy of -3.74 eV (Bi2S3: -3.98 eV, MnO2: -4.41 eV), underscoring its electronic suitability for radiosensitization. Additionally, MD simulations over 10,000 ps at 310 K demonstrated structural stability with a root-mean-square deviation (RMSD) of similar to 1.8-2.0 nm, dynamic flexibility with a root-mean-square fluctuation (RMSF) of similar to 0.15-0.3 nm, stable hydrogen bonding (similar to 2-3 bonds for MTX-MnO2-Bi2S3, radial distribution function peak at similar to 2.0 & Aring;), and compactness with a radius of gyration (R g) of similar to 0.5 nm for MTX and similar to 1.5 nm for MnO2-Bi2S3. These combined experimental and computational findings highlight the nanoplatform's potential to overcome tumor hypoxia, deliver MTX effectively, and enhance radiotherapy outcomes, offering a robust and innovative framework for synergistic cancer therapy and paving the way for future preclinical development.