Neuroblastoma (NB) is an embryonic tumor originating from the neural crest. The most well-defined genetic alteration in NB is the overexpression of the MYCN protein. PI3K/AKT/mTOR and AURORA signaling pathways play a role in MYCN stabilization, and abnormal activation of these pathways has been identified in NB. Nanoparticle (NP) drug delivery systems targeting tumor cells directly assist in the combined delivery of agents and reducing toxicity. In this study, the aim was to develop NPs that reduce the activity of mTOR and AURORA pathways, potentially decreasing MYCN protein enhancement and stability, by combining inhibitors and targeting them specifically to the tumor, and to demonstrate their effect in NB. Everolimus (EVER) and tozasertib (TOZA) encapsulated in NP and targeted with dinutuximab β (DTX-β). Experiments including viability, apoptosis, gene and protein expression determination were performed. DTX-β/EVER + TOZA@PEG-b(block)-PLGA NPs were successful to reduce the cell viability and to increase apoptosis. In vivo studies demonstrated notable tumor growth inhibition without organ toxicity. Elevated caspase expression and suppressed proteins indicated enhanced apoptosis and reduced oncogenic activity. DTX-β/EVER-TOZA@PEG-b-PLGA may exert cytotoxic and apoptotic effects in NB. The use of targeted nanocarriers in NB treatment may enhance cytotoxic and apoptotic responses specifically in the tumor region.
Biocompatibility is a critical requirement for nanoparticle-loaded mesenchymal stem cells (MSCs) used in targeted cancer therapy. This study aimed to evaluate the compatibility of carboplatin-loaded PEG–PLGA nanoparticles (CRB@PEG–PLGA) with adipose tissue-derived mesenchymal stem cells (ADSCs). CRB@PEG–PLGA nanoparticles were synthesized using a double emulsion solvent evaporation method and characterized by dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Isolated ADSCs were validated by surface marker expression and differentiation assays. Nanoparticle size, zeta potential, encapsulation efficiency (EE), and drug loading capacity (LC) were determined. Biocompatibility was assessed using a 24-hour MTT assay at increasing concentrations up to 7000 ng/mL. The nanoparticles exhibited a mean hydrodynamic diameter of 181.3 ± 9.07 nm, a zeta potential of − 14.1 ± 0.71 mV, an encapsulation efficiency of 66.4 ± 3.6
Hybrid multimodal imaging agents combining magnetic resonance imaging (MRI) and positron emission tomography (PET) capabilities offer potential for accurate tumor detection and monitoring. In our previous study, we synthesized manganese-loaded, mesoporous silica-coated superparamagnetic iron oxide nanoparticles functionalized with trastuzumab (Fe3O4-mSi-NH2-Mn-Tra), which demonstrated dual T1/T2 MRI contrast enhancement and selective cytotoxicity against HER2-positive breast cancer cells in vitro. In the current study, the nanoparticle was labeled with Zirconium-89 (89Zr) to evaluate its potential as a HER2-targeted PET imaging agent- candidate. Radiolabeling was performed using the p-isothiocyanatobenzyl-desferrioxamine (p-NCS-Bz-DFO) chelator, 89Zr-DFO-Fe3O4-mSi-NH2-Mn-Tra was labeled of 78 ± 2%. The labeled nanoparticles demonstrated high colloidal stability in PBS for up to 24 h and lipophilic (log P = 2.23 ± 0.24). In in vitro uptake studies, radiolabeled nanoparticles showed receptor-specific internalization in HER2-positive SKBR-3 cells (65.25% at 2 h), whereas the uptake was limited in HER2-negative MDA-MB-231 cells (20.22% at 4 h). When the receptor was blocked with trastuzumab, the uptake results was reduced by 11.14 ± 1.2%, confirming HER2-mediated binding. In vivo biodistribution studies in rats have shown that the radiolabeled nanoparticles accumulate in the reticuloendothelial organs (liver 15.53 ± 7.6% ID/g at 120 min) and renal excretion. These results suggest that 89Zr-DFO-Fe3O4-mSi-NH2-Mn-Tra nanoparticles may serve as a promising HER2-targeted PET/MRI candidate nanoplatform for further preclinical evaluation.
In this study, three Schiff base ligands (L1-L3) and their novel platinum(ii) complexes (I-III) were synthesized and characterized using FT-IR, NMR, and elemental analysis. The crystal structure of complex I was determined by X-ray crystallography, while the lipophilicity of the complexes was evaluated by UV-Vis spectroscopy. The ability of the compounds to inhibit A beta aggregation was assessed using the SH-SY5Y human neuroblastoma cell line. Due to its high cytotoxicity, comparable to that of cisplatin, complex II was excluded from further biological investigations. The kinetics of A beta aggregation inhibition were examined fluorometrically using Thioflavin-T, and the binding interactions of the complexes with the A beta 1-42 sequence were elucidated through studies of their interactions with l-histidine using 1H-NMR and LC/QTOF/MS analyses. The results demonstrate that complexes I and III significantly suppress A beta fibril formation, with IC50 values of 50 mu M and 25 mu M, respectively. The enhanced biological activity is attributed to the strong electron-donating properties of the ligand substituents. Overall, these findings reveal that the synthesized complexes effectively inhibit A beta amyloid aggregation and promote cell viability.
Pancreatic cancer remains one of the most aggressive malignancies with poor prognosis and limited treatment options. In view of the constraints imposed by current treatment modalities, there has been an increased focus on natural products as potential complementary agents in cancer therapy. Hypericum perforatum (HP), commonly known as St. John’s Wort, has demonstrated cytotoxic and apoptotic properties in various cancer models; however, its effects on pancreatic cancer cells are not well-studied. This study aimed to investigate the in vitro cytotoxic effects of Hypericum perforatum extract on AR42J pancreatic cancer cells. AR42J cells were cultured and treated with increasing concentrations (3.125–100 µg/mL) of HP extract for 24 and 48 hours. Cell viability was assessed using the MTT assay. Nuclear morphological changes were evaluated by DAPI staining and visualized with a Juli™ Smart Fluorescent Cell Analyzer. HP extract exhibited a dose- and time-dependent cytotoxic effect on AR42J cells. IC₅₀ values were determined to be 12.5 µg/mL at 24 hours and 6.25 µg/mL at 48 hours. DAPI staining confirmed nuclear condensation and fragmentation in treated cells, supporting apoptosis as a mechanism of action. These results indicate that H. perforatum extract effectively reduced pancreatic cancer cell viability while inducing apoptotic cell death. These findings suggest that H.perforatum extract exerts significant antiproliferative and pro-apoptotic effects on AR42J pancreatic cancer cells. The study highlights its potential as a plant- based complementary therapeutic candidate for pancreatic cancer treatment.
In this study, La1-xSrxMnO3 (x = 0.27, 0.3, 0.33) magnetic nanoparticles (MNPs) were synthesized and then these nanoparticles synthesized in the core-shell structure were coated with silane for potential magnetic hyperthermia applications. In order to provide support material for the coated magnetic nanoparticles, silane-coated hybrid magnetic nanoparticles were obtained by producing graphene oxide (GO) nanoflakes. The structural and magnetic properties and magnetothermal properties of these structures were investigated. It was observed that the structure of the silane-coated magnetic nanoparticles remained intact and did not show any degradation compared to the uncoated materials. In addition, the highest saturation magnetization (MS) value was observed in the sample doped with x = 0.30. This value indicated that the heating power would be higher than the other doped samples in the specific absorption ratio (SAR) measurements. In this context, the heating amount in the silane-coated samples showed a slight decrease compared to the uncoated samples. Despite the decrease in the SAR values of the integrated samples by incorporating GO into the coated MNPs, it is anticipated that effective results will be obtained for practical applications with the advantage of increasing the thermal conductivity of GO.
Studies on synthesizing MXene hybrid materials continue in medicine, biomedicine, the environment, electronics, and many other fields. MXenes are very remarkable materials for diagnosis, treatment, and theranostic applications in oncology with their hydrophilic structure, large surface area, and biocompatibility. In this study, MAX phase and Mo2CTx MXene syntheses were first carried out and characterized by XRD and HR-TEM. Then, PAH and fucoidan were coated on the MXene surface, respectively, and characterized by FE-SEM, XPS, and Zeta potential methods. Experiments on Mo2CTx-MXene@Fuc nanohybrids have identified their photothermal conversion capacity and photostability, which are crucial for photothermal therapy applications. After calibration of laser devices at 808 and 1064 nm, the nanohybrids' response to laser exposure was monitored, with temperature changes recorded via a thermal camera. Additionally, the photothermal conversion capacity was deduced from heating and cooling durations, while singlet oxygen production efficiency was evaluated using the 1,3-Diphenylisobenzofuran (DPBF) fluorescent probe. These findings underscore the potential of Mo2CTx-MXene@Fuc nanomaterials in photothermal therapy, particularly their efficiency in converting NIR radiation into therapeutic heat.
Magnetic nanoparticles are an important class of functional materials that have unique magnetic properties due to their reduced size (<100 nm) and have the potential for use in many fields. In the preparation of magnetic nanoparticles, factors such as intrinsic magnetic properties, surface coating, size and shape of the particles, surface charge and stability are very important. In this regard, carefully determining the synthesis parameters of magnetic nanoparticles and particle coating materials is of critical importance in the application area chosen for the material. In this study, La1-xSrxMnO3 (x = 0.27, 0.30, 0.33) magnetic nanoparticles (MNPs), carbon-coated magnetic nanoparticles in core-shell structure (C@MNP) and their derivatives integrated into graphene oxide (GO-C@MNP) were synthesized and their properties were investigated in detail for their use in possible future application studies. The crystal structure of perovskite compounds with Pbnm symmetry remains unchanged after carbon coating but shrinks in volume due to its amorphous structure. The magnetic behavior of the uncoated and coated materials is almost identical, but the Curie temperature of the compounds shifts to a higher temperature. In the specific absorption ratio (SAR) measurements performed, it was found that the best SAR value for carbon-coated MNPs was 12.9 W/g at x = 0.27. By integrating the MNPs into graphene oxide, heat is easily distributed regionally, and this shows that the structures can be ideal candidates for applications such as hyperthermia, drug carriers, tissue repair, and cellular therapy including cell labeling and targeting. Perovskite-structured manganite materials were selected for their suitability in controlled production, where the Curie temperature can be tuned near the therapeutic temperature by adjusting the doping levels, making them ideal for magnetic hyperthermia applications. In this study, for the first time, the nanoparticle surfaces were coated with carbon, which was chosen not only due to carbon's non-magnetic nature but also because it provides an ideal platform for future combined biomedical applications such as drug delivery systems.
This study examines the development and characterisation of manganese-loaded mesoporous silica-coated superparamagnetic iron oxide nanoparticles (Fe3O4-mSi-NH2-Mn) functionalized with trastuzumab for dualmode T1 and T2-weighted magnetic resonance imaging (MRI) applications in HER2-positive breast cancer. The synthesis process was confirmed through a series of analytical techniques, including Fourier Transform Infrared Spectroscopy (FTIR), Vibrating Sample Magnetometer (VSM), X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), and visualized with Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM) analyses. These analyses demonstrated that the nanoparticles had a controlled size, well-defined surface modifications, and superparamagnetic properties. In vitro evaluations showed that the Fe3O4-mSi-NH2-Mn-Tra nanoparticles effectively targeted HER2-positive SKBR3 human breast cancer cell lines, leading to significant cytotoxic effects at an IC50 concentration of 3.12 mu g/mL. Dual-mode imaging revealed that the incorporation of manganese resulted in enhanced T1-weighted signal intensities, while the superparamagnetic iron oxide core exhibited distinct T2 signal quenching. These multifunctional nanoparticles present a promising theranostic platform for precision cancer diagnostics and targeted therapy, offering an innovative solution to enhance imaging and treatment outcomes in HER2-positive breast cancer.
AIMS:The study aimed to evaluate the multifunctional therapeutic potential of PTX/Mo2CTx-MXene@Fuc combinations, emphasizing their performance in drug loading, release kinetics, oxidative stress induction, apoptosis, cell migration, and angiogenesis inhibition in cancer therapy. METHODS/MATERIALS:Mo2CTx-MXene@Fuc were synthesized and loaded with the chemotherapeutic drug Paclitaxel (PTX) to achieve pH- and NIR-responsive release. In vitro cytotoxicity, ROS generation, apoptosis, migration, and tube-formation assays were performed on cancer (4T1, MDA-MB-231) and normal (L929) cell lines under NIR (808 nm) irradiation. RESULTS:The nanosheets exhibited high PTX loading efficiency (85-90%) and pH-sensitive drug release, with accelerated release in acidic tumor-mimicking environments. NIR irradiation significantly enhanced ROS production in cancer cells while maintaining low oxidative activity in normal cells. Apoptosis assays confirmed pronounced cell death under NIR+ conditions, while migration and tube-formation analyses revealed that MXene nanosheets moderately inhibited cell motility and suppressed endothelial angiogenesis. These results demonstrated synergistic enhancement of photothermal, photodynamic, and chemotherapeutic effects. CONCLUSION:The findings indicate that PTX/Mo2CTx-MXene@Fuc nanosheets function as a multifunctional nanoplatform combining chemo-, photothermal-, and photodynamic-therapy mechanisms. Their selective cytotoxicity, ROS-mediated apoptosis, and anti-angiogenic activity highlight their strong potential for future targeted cancer therapy applications.
This study investigates the therapeutic potential of a nanohybrid structure, GO/C-TMZ@PmAb MNP, for targeted glioblastoma treatment by integrating chemotherapy with magnetic hyperthermia. Characterization of the nanohybrid confirmed successful conjugation of Panitumumab (PmAb) and effective loading of Temozolomide (TMZ), ensuring targeted delivery to glioblastoma cells. In vitro experiments demonstrated enhanced cytotoxicity and a significant increase in late-stage apoptosis in U-87 MG and U-251 MG glioblastoma cell lines, particularly when combined with an alternating magnetic field (AMF), highlighting the synergistic effect of combined therapy. Cellular uptake studies via ICP-OES and fluorescence microscopy revealed maximum uptake at 6 h postincubation. In vivo studies using a subcutaneous U-251 MG tumor model showed substantial inhibition of tumor growth, increased necrosis, and apoptosis rates, as well as reduced EGFRvIII expression in treated groups. Notably, the GO/C-TMZ@PmAb + AMF group exhibited the greatest therapeutic effect, with controlled tumor growth and minimal systemic toxicity observed in healthy organs. These results underscore the efficacy of the GO/C-TMZ@PmAb MNP nanohybrid in enhancing glioblastoma treatment through targeted drug delivery and hyperthermia, providing a promising platform for further preclinical and clinical investigations.
This study aimed to radiolabel elmalienoside A, a saponin-based adjuvant, with iodine-131 and evaluate its in vivo biodistribution. [131I]iodoelmalienoside A was prepared by the iodogen method and intravenously administered to Balb/C mice. Organ-specific uptake (
Triple-negative breast cancer (TNBC) is an aggressive tumor subtype that is resistant to conventional therapies due to the lack of targetable receptors. In this study, a paclitaxel (PTX)-loaded Mo2C@C@Fuc/Mo2C-MXene@Fuc hybrid nanosystem was developed, and the efficacy of a combined therapeutic approach, photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy (CT) was evaluated in vitro and in vivo against TNBC. The PTX/Mo2C@C@Fuc/Mo2C-MXene@Fuc hybrid nanosystem exhibited high drug loading efficiency and stimuli-responsive release. At 96 h, PTX release reached 58.6% at pH 4.5 and 44.2% at pH 6.0, while NIR irradiation further enhanced the release to 66.3% and 51.0%, respectively, confirming the pH- and light-responsive drug delivery capability of the system. Under NIR irradiation (808 nm), the hybrid structure generated significant levels of reactive oxygen species (ROS), leading to pronounced apoptotic induction and reducing cell viability to 52.8% in 4T1 cells. Similarly, in MDA-MB-231 cells, NIR-assisted combination treatment decreased viability to 55.9%. In contrast, L929 normal fibroblast cells retained a viability of 75.4% under the same treatment conditions, indicating cytotoxicity. Tube formation assay results demonstrated that the hybrid system significantly inhibited vascular structure formation in HUVEC cells after 24 h of incubation. In vivo studies further confirmed that the PTX-loaded hybrid system combined with NIR irradiation induced 82% necrosis and 12.5% apoptosis within tumor tissues, ultimately resulting in complete macroscopic tumor regression. Overall, this study highlights the potential of Mo2C-MXene-based hybrid nanostructures as a biocompatible and therapeutic platform for synergistic PDT/PTT/CT combination therapy in TNBC treatment.
This study evaluates the therapeutic potential of fucoidan-functionalized molybdenum carbide (Mo₂C@C@Fuc) nanospheres and their combination with paclitaxel (PTX) for targeted cancer therapy, with a focus on triple-negative breast cancer (TNBC) cell lines. The nanospheres exhibited 85-90 % drug-loading efficiency and pH-responsive release, ensuring enhanced delivery in acidic tumor microenvironments. Reactive oxygen species (ROS) assays revealed significant ROS generation under near-infrared (NIR) irradiation, particularly in the PTX/Mo₂C@C@Fuc group, selectively inducing oxidative stress in TNBC cells (4T1 and MDA-MB-231) while sparing healthy fibroblasts (L929). Apoptosis analyses confirmed increased cell death rates under NIR+ conditions, while migration assay demonstrated the nanospheres' ability to inhibit cancer cell migration and disrupt endothelial tube formation, respectively. These findings highlight the synergistic photothermal, photodynamic, and chemotherapeutic effects of Mo₂C@C@Fuc nanospheres, positioning them as a versatile and effective nanoplatform for advanced cancer therapy targeting triple-negative breast cancer.
MXenes, a member of the two-dimensional (2D) material family, and their hybrid structures have been the subject of considerable interest due to their unique properties, including a high surface area, chemical stability, and hydrophilicity. Due to their properties, application studies continue in medicine, biomedical, environment, and many other fields. MXenes are currently being utilized extensively in photothermal therapy (PTT) and photodynamic therapy (PDT) applications, and they have attracted considerable interest due to their efficacy in this field. In this study, the synthesis of Mo2C@C@Fuc/Mo2C-MXene@Fuc hybrid structures was performed. The resulting hybrid structure was then coated with poly (allylamine hydrochloride) (PAH) and fucoidan (Fuc), respectively. The synthesized hybrid structure was characterized by techniques such as FE-SEM, XPS, and Zeta potential. The photothermal conversion capacity and photostability of Mo2C@C@Fuc/Mo2C-MXene@Fuc nanohybrids have been demonstrated through experimentation, which are essential characteristics for their potential use in PTT. Moreover, the photothermal conversion capacity was calculated based on the heating and cooling durations, whereas the singlet oxygen production efficiency was evaluated using the 1,3-diphenylisobenzofuran (DPBF) fluorescent probe, which was also utilized as a PDT agent. These findings highlight the potential of Mo2C@C@Fuc/Mo2C-MXene@Fuc hybrid structures in photothermal therapy, particularly their efficacy in converting near-infrared radiation into therapeutic heat. Additionally, their potential for photodynamic therapy (PDT) has been demonstrated through ROS generation.
Mo2C structure, a transition metal carbide, is known for its exceptional properties including high chemical and thermal stability and surface activity. Recently, carbon-modified Mo2C structures have found widespread applications due to their effectiveness. Here, we synthesized pomegranate-like Mo2C@C nanospheres and coated them with poly(allylamine hydrochloride) (PAH) and fucoidan structures. Characterization techniques including FE-SEM, HR-TEM, XRD, XPS, and zeta potential analysis were employed. We investigated the effect of Mo2C@C@Fuc nanospheres by quantitatively evaluating their photothermal conversion efficiency. Under irradiation at wavelengths of 808 nm and 1064 nm with a power intensity of 2 W/cm2, these nanospheres could convert up to 15 % of the incident laser energy into heat, outperforming conventional materials. Stability tests in various physiological pH environments confirmed their durability under NIR irradiation, ensuring operational integrity in biological environments. In addition, they showed significant efficiency in the production of singlet oxygen, making them promising agents for PDT. Biodegradation studies indicated safe degradation after ther- apeutic application, highlighting their environmental and physiological compatibility. Integrating Mo2C@C@- Fuc nanospheres into anticancer strategies combines the advantages of PTT and PDT, promising improved therapeutic outcomes with high biocompatibility.
This study explores the therapeutic potential of a novel nanohybrid structure, C-TMZ@PmAb MNP, designed for targeted glioblastoma treatment through the combination of chemotherapy and magnetic hyperthermia. Comprehensive characterization of the nanohybrid revealed successful conjugation of Panitumumab (PmAb) and effective temozolomide (TMZ) loading, demonstrating enhanced apoptotic activity in glioblastoma cell lines (U-87 MG and U-251 MG MG). Cellular uptake studies were confirmed by both ICP-OES and fluorescence microscopy, with the peak of uptake occurring at 6 h post-incubation. Apoptosis assays showed a significant increase in late apoptosis in glioblastoma cells treated with the nanohybrid, especially when combined with an alternating magnetic field (AMF), confirming the synergistic effect of the combined therapy. Additionally, EGFR expression analysis indicated a decrease in expression levels following treatment with C-TMZ@PmAb MNP. These findings suggest that the C-TMZ@PmAb MNP nanohybrid effectively enhances therapeutic efficacy against glioblastoma by leveraging targeted drug delivery and hyperthermia, thus warranting further investigation for clinical applications.
During Gallium 68Ga-PSMA PET prostate imaging, the kidneys and liver tissue is the uptake amount of radioactive. The doses in the critical organs should be well determined due to the toxic effects of radiation exposure on the human body. The absorbed dose distribution in the liver and kidneys for 68Ga activity data and absorbed dose values were calculated using Phantom TLD, Monte Carlo EGSnrc, and the IDAC Dose software for the TLD settings. It was calculated that 1.3E-2 mGy/MBq and 3E-1 mGy/MBq in the Phantom TLD, 0.7E-2 mGy/MBq, and 4.5E-2 mGy/MBq in the IDAC Dose, and 0.8E-1 mGy/MBq and 0.9E-2 mGy/MBq in the EGSnrc simulation for dose per unit activity in MBq.
Wound dressing materials are crucial for accelerating the healing period of chronic wounds. In this study, chitosan nanoparticles loaded with Hypericum perforatum (Hp) were modified with agarose to create wound-healing films and their antimicrobial potential was investigated in vitro. Chitosan (CS) nanoparticles and Hp-loaded nanoparticles were prepared using the ionic gelation method. The synthesized Hp-loaded CS nanoparticles were modified with agarose by the solvent-casting method. Antimicrobial assays were performed using the disk diffusion method and agar well diffusion method. The characterization of nanoparticles and films was performed by UV-Vis spectrophotometry, Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR), mechanical testing, and swelling testing. The results showed that Hypericum perforatum was loaded into chitosan nanoparticles with a 90.1 +/- 2.53 % yield. The sizes of the Hypericum perforatum-loaded chitosan nanoparticles and chitosan nanoparticles were 156 +/- 22 nm and 69 +/- 4.2 nm, respectively. The CS-Hp/Agarose film showed no cytotoxic effect on L929 fibroblast cells and maintained cell viability for 72 h. These results indicate that Hp might be used in wound healing due to its antimicrobial and cell growth-promoting properties.