Drug Cisplatin Research Articles

Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors.

Strategies to enhance the anti-tumor immune response of stereotactic ablative radiotherapy (SABR) at primary tumors and abscopal sites are under intensive investigation. Here we report a metabolizable binary supracluster (BSCgal) that combines gold nanoclusters as radiosensitizing adjuvants with small interfering RNA (siRNA) targeting the immunosuppressive mediator galectin-1 (Gal-1). BSCgal comprises reversibly crosslinked cationic gold nanoclusters and siRNA complexes in a polymer matrix that biodegrades over weeks, facilitating clearance (90.3% in vivo clearance at 4 weeks) to reduce toxicity. The particle size well above the renal filtration threshold facilitates passive delivery to tumors. Using mouse models of head and neck cancer, we show that BSCgal augments the radiodynamic and immunotherapeutic effects of SABR at the primary and metastatic tumors by promoting tumor-inhibitory leukocytes, upregulating cytotoxic granzyme B and reducing immunosuppressive cell populations. It outperforms SABR plus Gal-1 antagonists, chemoradiation drug cisplatin or PD-1 inhibitor. This work presents a translatable strategy to converge focal radiosensitization with targeted immune checkpoint silencing for personalized radioimmunotherapy.

FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia.

We focused on the FOXN3 gene and selected its antisense transcripts (FOXN3-AS1) to investigate its potential involvement in acute myeloid leukemia (AML). Several integrated multi-omics datasets have expanded the horizons of the cancer landscape. With the emergence of new high-throughput technologies, a large number of non-coding RNAs have been confirmed to be involved in the pathogenesis of different types of hematological malignancies. We conducted experimental validation using quantitative polymerase chain reaction (qPCR) with bone marrow specimens from AML patients. Then, Kaplan-Meier (KM) and Receiver Operating Characteristic (ROC) curves were used to substantiate the prognostic association between FOXN3-AS1 and AML patients within the TCGA database. Correlation between FOXN3-AS1 expression and gene mutation, immune, and immune function using Spearman correlation analysis. To explore the physical and functional interaction between FOXN3-AS1 and the DNMT1 protein, we utilized the RPISeq web tool from Iowa State University. Subsequently, we performed qPCR experiments to test the effect of 5AzaC (DNMT1 inhibitor) on FOXN3-AS1 expression AML cell lines (THP1 and OCI-AML3). We leveraged the "OncoPredict" R package in conjunction with the Genomics of Drug Sensitivity (GDSC) database to predict drug response in AML patients expressing FOXN3-AS1. We observed a significant upregulation of FOXN3-AS1 expression in AML patients compared to healthy controls using clinical samples. The TCGA database revealed an association between high FOXN3-AS1 expression and adverse prognosis. In our subsequent analysis, genes with poor prognostic implications in AML patients were exclusively identified in the FOXN3-AS1 high-expression group, further corroborating this relationship. AML patients with higher FOXN3-AS1 expression levels may respond less optimally to immunotherapy than patients with lower levels. Besides, we computationally predicted the interaction of FOXN3- AS1 and DNMT1 protein and experimentally confirmed that DNMT1i (GSK-3484862) affects the expression level of FOXN3-AS1. We also found that the chemotherapy drugs (5-Fluorouralic, Cisplatin, Dactolisib, Sapitinib, Temozolomide, Ulixertinib, Vinorelbine, Ruxolitinib, Osimertinib and Cisplatin) showed favorable responses in AML patients with high FOXN3-AS1 expression levels. Our candidate approach identifies FOXN3-AS1 as a prognostic indicator of survival in AML with a potential immune-related role. The preliminary observations we made on FOXN3-AS1/DNMT1 crosstalk warrant more in-depth invested immunotherapeutic approaches in AML.

Ironing Out the Kinks: Arming Natural Killer Cells against Ovarian Cancer.

Ameliorating the tumor immune microenvironment is a key strategy to improve the therapeutic outcomes of patients with cancer. Sandoval and colleagues demonstrate that iron chelation enhances type I IFN production, promotes NK cell tumor trafficking and activation, and synergizes with chemotherapy drug cisplatin to reduce metastatic ovarian cancer progression in murine models. See related article by Sandoval et al., p. 1901.

Cisplatin induces kidney damage through the down-regulation of Prx I by autophagic degradation

In this study, we investigated the potential role of PrxI in cis-diamminedichloroplatinum (cisplatin)-induced renal damage in mice. The anticancer drug cisplatin is a chemotherapeutic agent that is widely used to treat solid tumors. Cisplatin-induced nephrotoxicity is a serious dose-limiting side effect, primarily caused by oxidative stress. The oxidative stress further damages DNA, membranes, and mitochondria, and increases endoplasmic reticulum (ER) stress. Cisplatin produces reactive oxygen species (ROS) through Cytochrome P450 2E1 (CYP2E1) and localizes to the surface of the ER, where CYP2E1 is located.Among the six Prx isoforms, Prx I was selectively degraded in cisplatin-treated kidneys during severe renal function damage. Prx I degradation is blocked in mouse proximal tubular cells treated with 3-methyladenine, an autophagy inhibitor, and in MEF lacking ATG7. Moreover, increased ROS levels on the ER surface due to CYP2E1 overexpression further accelerated Prx I degradation. These results suggest that Prx I degradation is largely mediated through autophagy, which is promoted by cisplatin-induced ER stress. Ablation of Prx I exacerbated cisplatin-induced nephrotoxicity and significantly increased the abundance of oxidative stress, ER stress, and inflammatory markers in the kidney, indicating that Prx I plays a protective role against cisplatin-induced nephrotoxicity.

KDM1A/LSD1 inhibition enhances chemotherapy response in ovarian cancer.

Ovarian cancer (OCa) is the deadliest of all gynecological cancers. The standard treatment for OCa is platinum-based chemotherapy, such as carboplatin or cisplatin in combination with paclitaxel. Most patients are initially responsive to these treatments; however, nearly 90% will develop recurrence and inevitably succumb to chemotherapy-resistant disease. Recent studies have revealed that the epigenetic modifier lysine-specific histone demethylase 1A (KDM1A/LSD1) is highly overexpressed in OCa. However, the role of KDM1A in chemoresistance and whether its inhibition enhances chemotherapy response in OCa remains uncertain. Analysis of TCGA datasets revealed that KDM1A expression is high in patients who poorly respond to chemotherapy. Western blot analysis show that treatment with chemotherapy drugs cisplatin, carboplatin, and paclitaxel increased KDM1A expression in OCa cells. KDM1A knockdown (KD) or treatment with KDM1A inhibitors NCD38 and SP2509 sensitized established and patient-derived OCa cells to chemotherapy drugs in reducing cell viability and clonogenic survival and inducing apoptosis. Moreover, knockdown of KDM1A sensitized carboplatin-resistant A2780-CP70 cells to carboplatin treatment and paclitaxel-resistant SKOV3-TR cells to paclitaxel. RNA-seq analysis revealed that a combination of KDM1A-KD and cisplatin treatment resulted in the downregulation of genes related to epithelial-mesenchymal transition (EMT). Interestingly, cisplatin treatment increased a subset of NF-κB pathway genes, and KDM1A-KD or KDM1A inhibition reversed this effect. Importantly, KDM1A-KD, in combination with cisplatin, significantly reduced tumor growth compared to a single treatment in an orthotopic intrabursal OCa xenograft model. Collectively, these findings suggest that combination of KDM1A inhibitors with chemotherapy could be a promising therapeutic approach for the treatment of OCa.

Unveiling novel drug delivery mechanism: Cisplatin’s bonding behaviour with BC4N Nanostructure

Recent advancements in nanotechnology have opened avenues to address the selectivity challenges in targeted drug delivery systems, minimizing adverse effects. While carbon nanotubes (CNTs) have gained traction as drug carriers, their B, N-containing counterpart, pristine boron carbonite (p-BC4N), remains underexplored. This study investigates the possibility of pristine boron carbonite (p-BC4N) nanotubes as a drug carrier for the anticancer medication cisplatin (CPT). Using first-principles Density Functional Theory (DFT) simulations, we examined the interaction between CPT and p-BC4N nanotubes, revealing favourable adsorption energies (−0.523 eV) due to orbital interactions and charge transfer between the C 2p orbitals of BC4N and the 1 s orbitals in H of CPT. Ab initio molecular dynamics (AIMD) simulations confirmed the stability of the system at room temperature. Furthermore, pH and temperature-dependent desorption measurements demonstrated the effectiveness of p-BC4N nanotubes as a promising candidate for CPT drug delivery, highlighting their potential in targeted cancer therapy. This work opens up new avenues for the development of nanotechnology-based drug delivery systems.

BUB1 Inhibition Overcomes Radio- and Chemoradiation Resistance in Lung Cancer.

Background: Despite advances in targeted therapies and immunotherapies, traditional treatments like microtubule stabilizers (paclitaxel, docetaxel), DNA-intercalating platinum drugs (cisplatin), and radiation therapy remain essential for managing locally advanced and metastatic lung cancer. Identifying novel molecular targets could enhance the efficacy of these treatments. Hypothesis: We hypothesize that BUB1 (Ser/Thr kinase) is overexpressed in lung cancers and its inhibition will sensitize lung cancers to chemoradiation. Methods: BUB1 inhibitor (BAY1816032) was combined with cisplatin, paclitaxel, a PARP inhibitor olaparib, and radiation in cell proliferation and radiation-sensitization assays. Biochemical and molecular assays evaluated the impact on DNA damage signaling and cell death. Results: Immunostaining of lung tumor microarrays (TMAs) confirmed higher BUB1 expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) compared to normal tissues. In NSCLC, BUB1 overexpression correlated directly with the expression of TP53 mutations and poorer overall survival in NSCLC and SCLC patients. BAY1816032 synergistically sensitized lung cancer cell lines to paclitaxel and olaparib and enhanced cell killing by radiation in both NSCLC and SCLC. Molecular analysis indicated a shift towards pro-apoptotic and anti-proliferative states, evidenced by altered BAX, BCL2, PCNA, and Caspases-9 and -3 expressions. Conclusions: Elevated BUB1 expression is associated with poorer survival in lung cancer. Inhibiting BUB1 sensitizes NSCLC and SCLC to chemotherapies (cisplatin, paclitaxel), targeted therapy (olaparib), and radiation. Furthermore, we present the novel finding that BUB1 inhibition sensitized both NSCLC and SCLC to radiotherapy and chemoradiation. Our results demonstrate BUB1 inhibition as a promising strategy to sensitize lung cancers to radiation and chemoradiation therapies.

Insights into bismuthene and antimonene as cisplatin drug carriers: A theoretical comparative investigation

While effective targeted delivery is a challenge in nanomedicine for the delivery of anti-cancer drugs, this work focuses on the potential use of Bismuthene and antimonene nanosheets as nanocarriers for cisplatin anti-cancer using DFT methods. The results indicate that, compared to antimonene, bismuthene demonstrates significantly better physical stability, drug release rate, solubility, and biocompatibility, making it an excellent candidate for drug delivery systems. The parallel and perpendicular orientations of the anticancer drug were adsorbed on both nanosheets; the parallel configuration was the most energetically favored with an adsorption energy of −0.79 eV at the parallel site. A charge transfer from the drug to the bismuthene sheet is also revealed by the electronic charge analysis and DOS calculation, thus confirming efficient drug adsorption. Modeling a proton attack on the drug and the carrier surface near the adsorption sites was performed to model drug release, showing the stability and potential of bismuthene in this aspect of drug release mechanisms. Further, with an approach to studying its interactions with biomolecules, interactions of the drug molecule have been analyzed with amino acids, showing that drugs interact efficiently. Further assessments concerning work function, recovery time, electron localization function, and frontier molecular orbital analyses leave no doubt that bismuthene has beneficial features over antimonene. These thorough assessments present bismuthene as a more promising nanocarrier for the delivery of anti-cancer drugs and open a potential pathway to enhance the efficacy of strategies against cancer treatment.

Cytotoxic properties, glycolytic effects and high-resolution respirometry mitochondrial activities of Eriocephalus racemosus against MDA-MB 231 triple-negative breast cancer

IntroductionTriple-negative breast cancer (TNBC) represents a significant global health crisis due to its resistance to conventional therapies and lack of specific molecular targets. This study explored the potential of Eriocephalus racemosus (E. racemosus) as an alternative treatment for TNBC. The cytotoxic properties and high-resolution respirometry mitochondrial activities of E. racemosus against the MDA-MB 231 TNBC cell line were evaluated.MethodsHexane solvent and bioactive fraction extractions of E. racemosus were performed, while mass spectrometry-based metabolite profiling was used to identify the phytochemical constituents of the extracts. The extracts were further tested against MDA-MB 231 TNBC cells to determine their cytotoxicity. The mode of cell death was determined using flow cytometry. The activities of caspases 3, 8, and 9 were assessed using a multiplex activity assay kit. Glycolytic activity and High-resolution respirometry measurements of mitochondrial function in the MDA-MB 231 cell line were conducted using the Seahorse XFp and Oroboros O2K.ResultsMetabolite profiling of E. racemosus plant crude extracts identified the presence of coumarins, flavonoids, sesquiterpenoids, triterpenoids, and unknown compounds. The extracts demonstrated promising cytotoxic activities, with a half maximal inhibitory concentration (IC50) of 12.84 µg/mL for the crude hexane extract and 15.49 µg/mL for the bioactive fraction. Further, the crude hexane and bioactive fraction extracts induced apoptosis in the MDA-MB-231 TNBC cells, like the reference drug cisplatin (17.44%, 17.26% and 20.25%, respectively) compared to untreated cells. Caspase 3 activities confirmed the induction of apoptosis in both cisplatin and the plant crude extracts, while caspase 8 and 9 activities confirmed the activation of both the intrinsic and extrinsic apoptosis pathways. Increased levels of glycolytic activity were observed in the hexane crude extract. High-resolution respiratory measurements showed elevated mitochondrial activities in all mitochondrial states except for complex-IV activity.ConclusionThese findings support further exploration of E. racemosus as a potential therapeutic agent for TNBC, offering a promising avenue for the development of targeted treatments with minimal adverse effects.

Electrochemotherapy and Calcium Electroporation on Hepatocellular Carcinoma Cells: An In-Vitro Investigation

PurposeElectrochemotherapy, clinically established for treating (sub)cutaneous tumors, has been standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy (ESOPE). Due to common side effects of chemotherapeutic drugs, recent advances focus on non-cytotoxic agents, like calcium, to induce cell death (calcium electroporation). Therefore, this study aims to determine the efficacy of electrochemotherapy with bleomycin or cisplatin, or calcium electroporation on human hepatocellular carcinoma cells (HepG2) in vitro using the ESOPE protocol.MethodsHepG2 cell viability was measured with a MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after electrochemotherapy with the chemotherapeutic drugs bleomycin or cisplatin (0–20 µM), or after calcium electroporation (0–20 mM), to determine its efficacy on HepG2 cells in vitro using the ESOPE protocol (8 rectangular pulses, 1000 V/cm, 100 µs) compared to non-electroporated drug treatment.ResultsCell viability was significantly lower in electroporated samples, compared to their non-electroporated controls (27–75% difference). Electrochemotherapy with bleomycin and calcium electroporation, reached (almost) complete cell death (− 1 ± 3% and 2.5 ± 2%), in the lowest concentration of 2.5 µM and 2.5 mM, respectively. Electrochemotherapy with 2.5 µM cisplatin, significantly decreased cell viability to only 68% (± 7%).ConclusionElectrochemotherapy with bleomycin or cisplatin, or calcium electroporation were more effective in reducing the HepG2 cell viability in vitro using the ESOPE protocol compared to the non-electroporated drug treatments alone. When comparing electrochemotherapy, HepG2 cells are more sensitive to bleomycin than cisplatin, in similar concentrations. Calcium electroporation has the same effectiveness as electrochemotherapy with bleomycin, but calcium potentially has a better safety profile and several treatment advantages.Graphical

Design, Synthesis and Characterization of Mn(II)Cysteine-Tyrosine Dithiocarbamate Complex for against the Cancer on MCF-7 Breast Cancer Cell Line.

Breast cancer is the most frequently diagnosed cancer and the second cause of death worldwide. The drug often used for chemotherapy is cisplatin. However, the drug cisplatin has a number of problems, including lack of selectivity, undesirable side effects, resistance, and toxicity in the body. So research is carried out on new drug compounds with low toxicity by designing in silico with molecular docking. Mn(II) Cysteine-Tyrosine dithiocarbamate is a new complex molecule whose research involves several steps, such as in-silico molecular docking testing with target proteins, ADMET then synthesis, characterization and in-vitro MCF-7 cells for anticancer drugs. The synthesis process involves the reaction of manganese metal with tyrosine, cysteine, CS2 and KOH. Characterization tests have been carried out including FT-IR spectroscopy, SEM-EDS, UV Vis, conductivity, melting point and XRD. Confirm the structure of the compound using UV Vis, obtained orbitals π to π* and n to π* in the group N = C = S is represented by the absorption at 400 nm and 600 nm, FT-IR with the results obtained by the functional groups O-H, N-H, C =N and C=S. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting from 250 μg/mL and an IC50 value of 416.90 µg/mL. Molecular docking studies of the Mn(II)Cysteine-Tyrosine dithiocarbamate complex were identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α which showed an active site with amino acid residues GLU323, GLU385, VAL446, ILE514, TRP360, LYS449, MET388, MET357, PHE445, VAL392 and ILE389. Hydrophobic and hydrophobic bonds are seen in Mn(II)Cysteine-Tyrosine dithiocarbamate - Estrogen α has a bond energy of -77.5372 kJ/mol. Despite having a high H-bond interaction intensity, the chemical does not have a powerful enough anticancer impact. Despite the produced compound's low bioactivity, this study should offer important new understandings into how molecular structure affects anticancer activity.

FOXO1-NCOA4 Axis Contributes to Cisplatin-Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy.

Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage can also render cochlear implants ineffective. However, the mechanisms underlying cisplatin-induced SGNs damage and subsequent SNHL are still under debate and there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis is triggered in SGNs following exposure to cisplatin. Inhibiting ferroptosis protects against cisplatin-induced SGNs damage and hearing loss, while inducing ferroptosis intensifies these effects. Furthermore, cisplatin prompts nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in SGNs, while knocking down NCOA4 mitigates cisplatin-induced ferroptosis and hearing loss. Notably, the upstream regulator of NCOA4 is identified and transcription factor forkhead box O1 (FOXO1) is shown to directly suppress NCOA4 expression in SGNs. The knocking down of FOXO1 amplifies NCOA4-mediated ferritinophagy, increases ferroptosis and lipid peroxidation, while disrupting the interaction between FOXO1 and NCOA4 in NCOA4 knock out mice prevents the cisplatin-induced SGN ferroptosis and hearing loss. Collectively, this study highlights the critical role of the FOXO1-NCOA4 axis in regulating ferritinophagy and ferroptosis in cisplatin-induced SGNs damage, offering promising therapeutic targets for SNHL mitigation.

Modulation of blood-tumor barrier transcriptional programs improves intra-tumoral drug delivery and potentiates chemotherapy in GBM.

Glioblastoma (GBM) is the most common malignant primary brain tumor. GBM has an extremely poor prognosis and new treatments are badly needed. Efficient drug delivery to GBM is a major obstacle as the blood-brain barrier (BBB) prevents passage of the majority of cancer drugs into the brain. It is also recognized that the blood-brain tumor barrier (BTB) in the growing tumor represents a challenge. The BTB is heterogeneous and poorly characterized, but similar to the BBB it can prevent therapeutics from reaching effective intra-tumoral doses, dramatically hindering their potential. Here, we identified a 12-gene signature associated with the BTB, with functions related to vasculature development, morphogenesis and cell migration. We identified CDH5 as a core molecule in this set and confirmed its over-expression in GBM vasculature using spatial transcriptomics of GBM patient specimens. We found that the indirubin-derivative, 6-bromoindirubin acetoxime (BIA), could downregulate CDH5 and other BTB signature genes, causing endothelial barrier disruption in endothelial monolayers and BBB 3D spheroids in vitro. Treatment of tumor-bearing mice with BIA enabled increased intra-tumoral accumulation of the BBB non-penetrant chemotherapeutic drug cisplatin and potentiated cisplatin-mediated DNA damage by targeting DNA repair pathways. Finally, using an injectable BIA nanoparticle formulation, PPRX-1701, we significantly improved the efficacy of cisplatin in patient-derived GBM xenograms and prolonged their survival. Overall, our work reveals potential targets at the BTB for improved chemotherapy delivery and the bifunctional properties of BIA as a BTB modulator and potentiator of chemotherapy, supporting its further development.

Synergistic Strategies in Prostate Cancer Therapy: Electrochemotherapy and Electromagnetic Hyperthermia.

Prostate cancer is a significant global health problem, being the second most common cancer and the fifth leading cause of death in men worldwide. Standard chemotherapy, though effective, often lacks selectivity for tumor cells, resulting in dose-limiting side effects. To address this, innovative biomedical approaches such as electrochemotherapy and electromagnetic hyperthermia have emerged. Electrochemotherapy improves drug delivery by facilitating electroporation, thereby increasing intracellular concentrations of chemotherapeutic agents. This approach reduces dosages and associated adverse effects. Meanwhile, electromagnetic hyperthermia raises the temperature of tumor cells, enhancing their sensitivity to chemotherapy. While previous research has demonstrated the inhibitory effects of magnetic hyperthermia on prostate cancer cell growth both in vitro and in vivo, and its synergy with chemotherapy has shown enhanced tumor remission, limited studies have focused on electrochemotherapy alone or in combination with hyperthermia in prostate cancer models. This study aims to assess the synergistic effects of electromagnetic hyperthermia, with superparamagnetic iron oxide nanoparticles (SPIONs) and electrochemotherapy, with electroporation and the chemotherapeutic drugs bleomycin and cisplatin, on the prostate cancer-derived cell line DU-145/GFP and prostate-derived cell line RWPE-1. Results indicate enhanced cytotoxicity with both treatments (bleomycin and cisplatin) by adding electroporation, demonstrating a particularly pronounced effect with bleomycin. Combining electroporation with hyperthermia significantly augments cytotoxicity. Moreover, electroporation effectively reduced the time of exposure to electromagnetic hyperthermia while magnifying its cytotoxic effects. Future research in in vivo trials may reveal additional insights into the combined effects of these therapies.

Synthesis and characterization of nickel-based MOFs: Enhancing photocatalysis and targeted cancer drug delivery

Metal–organic frameworks (MOFs) are intricate molecular solids formed by connecting organic ligands with metal or metal–cluster binding sites. They have exceptional characteristics such as expansive surface area, adaptability, and meticulously structured porosity, rendering them valuable in various applications including photocatalytic degradation and drug delivery systems. In this investigation, a benign Ni-based MOF was synthesized using benzene 1,4dicarboxylic acid as a linker and dimethyl sulfoxide as a solvent through the hydrothermal approach within a Teflon autoclave. The synthesized MOFs were precisely characterized using techniques such as X-ray diffraction, scanning electron microscope with energy-dispersive X-ray analysis, Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis, and N2-sorption measurements. The photocatalytic efficiency of the Ni-based MOF was explored against Congo red under visible light exposure, with the proposed mechanism involving electron transfer from photoexcited organic ligands to metallic clusters, resulting in a degradation efficiency of 98.68 % after 145 min. Furthermore, the Ni-based MOFs, when loaded with the anticancer drug cisplatin, displayed notable capabilities in drug delivery against the human breast cancer cell line MDA-MB-231, leading to a 35.26 % reduction in cell viability. Cytotoxicity assessments using the MTT assay revealed that the nano-carriers hindered cell proliferation with an IC50 value of 46.84 μg/mL.

Green photoluminescence, supercapacitor and cytotoxic properties of nickel doped haematite nanoparticles

Fe2O3: Ni (1–9 mol.%) nanoparticles (NPs) were synthesized using the co-precipitation method and calcined at 500∘C for 12 h. The crystallite size, phase, crystallinity, and structural parameters were analyzed via powder X-ray diffraction. The Bragg reflections confirmed that the synthesized NPs crystallize in a pure hexagonal crystal structure with space group R-3c. Surface morphology analysis revealed agglomerated NPs of irregular sizes and shapes. Energy Dispersive X-ray Analysis confirmed the presence of Fe, O, and Ni elements, as well as the purity of the sample. Both the direct band gap energy and crystallite size decreased with increasing dopant concentration. Detailed studies were conducted on the photoluminescence and anticancer properties. The CIE coordinates indicated a color tuning from blue to green in the visible region. CIE coordinates and CCT values ranging between 2860 to 9547 k demonstrated that the synthesized nanophosphor material meets the requirements of display technology. Additionally, anticancer properties were investigated using HeLa cells and compared with the standard drug cisplatin for biomedical applications. Electrochemical investigations revealed super capacitance values ranging from 93.43 to 149.13 F/g at a scan rate of 10 mV/s with increasing Ni2+ concentration. Therefore, the synthesized Ni2+-doped hematite NPs show great promise in display technology, the biomedical field, and as supercapacitors in energy storage devices.

Induction of Ferroptosis by an Amalgam of Extracellular Vesicles and Iron Oxide Nanoparticles Overcomes Cisplatin Resistance in Lung Cancer.

Extracellular vesicles (EVs) hold potential as effective carriers for drug delivery, providing a promising approach to resolving challenges in lung cancer treatment. Traditional treatments, such as with the chemotherapy drug cisplatin, encounter resistance in standard cell death pathways like apoptosis, prompting the need to explore alternative approaches. This study investigates the potential of iron oxide nanoparticles (IONP) and EVs to induce ferroptosis-a regulated cell death mechanism-in lung cancer cells. We formulated a novel EV and IONP-based system, namely 'ExoFeR', and observed that ExoFeR demonstrated efficient ferroptosis induction, evidenced by downregulation of ferroptosis markers (xCT/SLC7A11 and GPX4), increased intracellular and mitochondrial ferrous iron levels, and morphological changes in mitochondria. To enhance efficacy, tumor-targeting transferrin (TF)-conjugated ExoFeR (ExoFeR TF ) was developed. ExoFeR TF outperformed ExoFeR, exhibiting higher uptake and cell death in lung cancer cells. Mechanistically, nuclear factor erythroid 2-related factor 2 (Nrf2)-a key regulator of genes involved in glutathione biosynthesis, antioxidant responses, lipid metabolism, and iron metabolism-was found downregulated in the ferroptotic cells. Inhibition of Nrf2 intracellular translocation in ExoFeR TF -treated cells was also observed, emphasizing the role of Nrf2 in modulating ferroptosis-dependent cell death. Furthermore, ExoFeR and ExoFeR TF demonstrated the ability to sensitize chemo-resistant cancer cells, including cisplatin-resistant lung cancer patient-derived tumoroid organoids. In summary, ExoFeR TF presents a promising and multifaceted therapeutic approach for combating lung cancer by intrinsically inducing ferroptosis and sensitizing chemo-resistant cells.

Dexamethasone reduces cisplatin-induced hair cell damage by inducing cisplatin resistance through metallothionein-2.

Hair cell damage is a common side effect caused by the anticancer drug cisplatin (CDDP), which reduces patient quality of life. One CDDP resistance mechanism that occurs in recurrent cancers is heavy metal detoxification by metallothionein-2 (mt2). Here, we show that in zebrafish larvae, dexamethasone (DEX) reduces CDDP-induced hair cell damage by enhancing mt2 expression. Transgenic zebrafish (cldn: gfp; atoh1: rfp) that express green and red fluorescent proteins in neuromasts and hair cells, respectively, were used. The zebrafish were pretreated with DEX at 52h post-fertilization (hpf) for 8h, followed by CDDP treatment for 12h. The lateral line hair cells of CDDP-treated zebrafish at 72hpf were observed by fluorescence microscopy. Reporting odds ratio (ROR) analysis using an adverse event database indicated an association between a decrease in CDDP-induced ototoxicity and DEX as an antiemetic treatment for cancer chemotherapy. Pretreatment with DEX protected 72hpf zebrafish hair cells from CDDP-induced damage. The expression of mt2 mRNA was significantly increased by the combination of 10µM DEX with CDDP. Gene editing of mt2 reversed the protective effect of DEX against CDDP-induced damage in hair cells. DEX protects hair cells from CDDP-induced damage through increased mt2 expression, which is a resistance mechanism for platinum-based anticancer drugs.

Photoluminescence, cytotoxic and oxygen evolution reaction kinetics studies of silver doped haematite nanoparticles

Fe2O3: Ag(1–9 mol %) nanoparticles (NPs) have been synthesized through the co-precipitation method. Crystallite size, phase, crystallinity, and structural parameters were analyzed by using powder X-ray diffraction. The Bragg reflections confirm that the synthesized NPs crystallize in hexagonal crystal structure with space group R-3c. Surface morphology consists of agglomerated irregular size and roughly spherical-shaped NPs. Energy Dispersive Analysis of X-ray confirms the presence of Fe, O, and Ag elements and also the purity of the sample. Crystallite size decreased with the increase in dopant concentration. Direct band gap energy is found to increase with an increase in dopant concentration. Photoluminescence and anticancer properties were studied in detail. The CIE coordinates confirm red emission in the visible region. CIE and CCT co-ordinate values indicate cool light emission, hence, the synthesized nanophosphor material meets the demand of display technology. Further anticancer properties were investigated on HeLa cells and compared with the standard drug cisplatin for biomedical applications. Further, Oxygen evolution reaction kinetics was investigated for Fe2O3:Ag (1 mol %) nanoparticles. demonstrates enhanced oxygen evolution reaction performance with a low overpotential of 348 mV, as shown by linear sweep voltammetry. It also exhibits a favorable Tafel slope of 83 mV/dec, indicating efficient electron transfer kinetics, making it a promising candidate for OER applications.

Patterned PVA Hydrogels with 3D Petri Dish® Micro-Molds of Varying Topography for Spheroid Formation of HeLa Cancer Cells: In Vitro Assessment.

Cell spheroids are an important three-dimensional (3D) model for in vitro testing and are gaining interest for their use in clinical applications. More natural 3D cell culture environments that support cell-cell interactions have been created for cancer drug discovery and therapy applications, such as the scaffold-free 3D Petri Dish® technology. This technology uses reusable and autoclavable silicone micro-molds with different topographies, and it conventionally uses gelled agarose for hydrogel formation to preserve the topography of the selected micro-mold. The present study investigated the feasibility of using a patterned Poly(vinyl alcohol) hydrogel using the circular topography 12-81 (9 × 9 wells) micro-mold to form HeLa cancer cell spheroids and compare them with the formed spheroids using agarose hydrogels. PVA hydrogels showed a slightly softer, springier, and stickier texture than agarose hydrogels. After preparation, Fourier transform infrared (FTIR) spectra showed chemical interactions through hydrogen bonding in the PVA and agarose hydrogels. Both types of hydrogels favor the formation of large HeLa spheroids with an average diameter of around 700-800 µm after 72 h. However, the PVA spheroids are more compact than those from agarose, suggesting a potential influence of micro-mold surface chemistry on cell behavior and spheroid formation. This was additionally confirmed by evaluating the spheroid size, morphology, integrity, as well as E-cadherin and Ki67 expression. The results suggest that PVA promotes stronger cell-to-cell interactions in the spheroids. Even the integrity of PVA spheroids was maintained after exposure to the drug cisplatin. In conclusion, the patterned PVA hydrogels were successfully prepared using the 3D Petri Dish® micro-molds, and they could be used as suitable platforms for studying cell-cell interactions in cancer drug therapy.