Efficiency of the zinc chelator 1,10-phenanthroline for assisted oocyte activation following ICSI in pigs.

Context In vitro embryo production in pigs is an important tool for advancing biomedical research. Intracytoplasmic sperm injection (ICSI) circumvents the polyspermy problems associated with conventional IVF in porcine. However, the suboptimal efficiency for ICSI in pigs requires new strategies to increase blastocyst formation rates. Aim To investigate novel methods for assisted activation using the zinc chelator 1,10-phenanthroline (PHEN), and to improve embryo developmental competence and quality of ICSI porcine blastocyst. Methods ICSI embryos were treated with PHEN after or before sperm injection, recording pronuclear formation, blastocyst rate and the expression of SMARCA4, OCT4, SOX2 and CDX2. Key results Neither electrical nor PHEN significantly improves pronuclear formation rates before or after ICSI. Following in vitro culture to the blastocyst stage, no significant differences were observed in developmental rates among the groups. Moreover, the use of PHEN did not alter the total cell number or the expression of OCT4, SOX2 and CDX2 in pig ICSI blastocysts. Conclusions Assisted oocyte activation with PHEN does not affect the preimplantation development of ICSI-derived pig embryos. Implications These results hold significance in refining and advancing the application of assisted oocyte activation techniques. They offer insights into addressing fertility issues and propelling advancements in human and animal reproductive medicine.

Unveiling the Versatility of Coumarin-Integrated with Phenanthroline/Thiabendazole-Based EuIII Complexes for Smart LEDs, Vapoluminescence, and Bioimaging Applications.

Narrow band red-emitting phosphors based on organo-Eu(III) complexes prove their energetic features with surprising performance in smart red/white LEDs, sensing, and biological fields. In this report, a series of unique Eu(III) complexes have been synthesized with coumarin integrated with a class of phenanthroline(Phen)/thiabendazole(TBZ) based ancillary ligands and dibenzoyl methane (DBM)/2-theonyl trifluoroacetone (TTA) as an anionic ligand. The computational study reveals that the TBZ/Phen-based neutral ligands are superior energy harvesters to those other reported analogue neutral ligands. All the Eu-complexes demonstrated outstanding red emission due to electric dipole (ED) transition (5D0 → 7F2) in solid, solution, and thin film with high quantum yield (QY). Theoretical analysis (TD-DFT) and experimental findings describe that the energy transfer (ET) from the ligand's triplet level to the Eu(III) ion is completely occurring. The Eu(III) complexes can potentially be used to fabricate intense hybrid white and red LEDs. All of the fabricated red LEDs revealed high luminous efficiency of radiation (LER) values. The fabricated blue LED based hybrid white LEDs displayed remarkable performance with a low correlated color temperature (5634 K), high color rendering index 88%, and CIE values (x = 0.33; y = 0.342) for 3Eu. By interaction with acid-base vapors, Eu-complexes displayed effectively alterable on-off-on luminescence. Further, cellular imaging shows that Eu-complexes can be a potential biomarker for cancer cell lines.

Efficient synthesis of novel 1,10 phenanthroline-substituted imidazolium salts: Exploring their anticancer applications.

This study reports a new series of 1,10-phenanthroline-substituted imidazolium salts (1a-f), examining their design, synthesis, structure and anticancer activities. The structures of these salts (1a-f) were characterized using 1H, 13C NMR, elemental analysis, mass spectrometry and Fourier transform infrared (FT-IR) spectroscopies. The salts' cytotoxic activities were tested against cancer cell lines, specifically MCF-7, MDA-MB-231 and non-tumorigenic MCF-10A mammary cells. The study compared the impact of aliphatic and benzylic groups in the salts' structure on their anticancer activity. Screening results revealed that compound 1c, in particular, showed promising inhibitory activity against the growth of MDA-MB-231 breast cancer cells, with an IC50 value of 12.8 ± 1.2 µM, indicating its potential as a chemotherapeutic agent. Cell apoptosis analysis demonstrated a tendency for compound 1c to induce early apoptosis in breast cancer cells. The stability/aquation of compound 1c was investigated using 1H NMR spectroscopy and its binding modes with DNA were explored via UV-Vis spectroscopy. Additionally, the study investigated the interaction residues and docking scores of compound 1c and the reference drug doxorubicin against Bax and Bcl-2 proteins using molecular docking.

Plumbagin's Antiproliferative Mechanism in Human Cancer Cells: A Copper-Dependent Cytotoxic Approach.

Cancer is a serious global health problem, causing the loss of millions of lives each year. Plumbagin, a compound derived from the medicinal plant Plumbago zeylanica, has shown promise in stopping the growth of tumor cells both in laboratory settings and in living organisms. Many plant-based compounds exert their effects through copper's ability to produce reactive oxygen species (ROS). This study aimed to understand how plumbagin, dependent on copper, induces cell death (apoptosis) in human cancer cells through various experiments. The results demonstrate that plumbagin hinders the growth of pancreatic cancer cells PNAC-1 and MIA PaCa-2 by utilizing the copper naturally present in the cells. Unlike metal chelators that remove iron and zinc (desferrioxamine mesylate and histidine), a specific copper chelator called neocuproine lessens the cell death caused by plumbagin. When ROS scavengers are used, plumbagin-induced apoptosis is inhibited, indicating that ROS plays a role in initiating cell death. The study also proves that plumbagin prevents copper from leaving cancer cells by suppressing the expression of specific genes (CTR1 and ATP7A). It is confirmed that plumbagin targets the nuclear copper, leading to signals that promote oxidative stress and, ultimately, cell death. These findings provide valuable insights into the potential of plumbagin as a substance to combat cancer, highlighting the importance of understanding how copper behaves within cancer cells.

The [(bathophenanthroline)3:Fe2+] complex as an aromatic non-polymeric medium for purification of human lactoferrin.

We describe a non-chromatographic, ligand-free platform for the efficient purification of recombinant human lactoferrin (LF). The platform consists of a [metal:chelator] complex precipitate in the presence of osmotically active polyethylene glycol 6000 (PEG-6000). Purification is achieved in three stages. Following formation of the complex, LF is captured under neutral conditions by the aggregated complexes (Step I), a washing step follows (Step II) and then, (Step III) LF is extracted in pure form with 100 mM tribasic Na citrate buffer (pH 7). Of the four complexes investigated, [bathophenanthroline (batho)3:Fe2+] was determined to be the most efficient. LF is recovered with high yield (∼90%, by densitometry) and purity (≥97%, by SDS polyacrylamide gel electrophoresis (SDS-PAGE)) from an artificial contamination background comprising E. coli lysate proteins. Purified LF is demonstrated to be monomeric by dynamic light scattering (DLS); to preserve its native secondary structure by circular dichroism (CD) spectroscopy; and, as apo-LF, to efficiently inhibit bacterial growth. Process yield is not affected by a 45-fold increase in LF concentration from 0.2 to 9 mg/mL. We provide evidence that protein capture relies on [cation:π] interactions between the lysine and arginine residues of LF with the fully aromatic [(batho)3:Fe2+] complexes. The use of [metal:chelator] complex aggregates is demonstrated to provide an economical and efficient avenue for LF purification.

Investigation of antitumor activity and albumin interaction of new sulfosalicylate-based complex by spectroscopic and computational approaches.

In the present study, the drug delivery by albumin protein and antiproliferetaive activity of new transition metal complex i.e., [Pd (phen)(SSA)] (where phen and SSA represent 1, 10 phenanthroline and sulfosalicylic acid, respectively) was investigated. DFT (density functional theory) calculations were conducted at B3LYP level with 6-311G(d,p)/aug-ccpVTZ-PP basis set for the purpose of geometry optimization, frontier molecular orbital (FMO) analysis, molecular electrostatic potential (MEP), and natural bond orbital (NBO) analysis. Experimental tests were conducted to preliminarily assess the lipophilicity and antitumor activity of the metal complex, resulting in promising findings. In-silico prediction was accomplished to assess its toxicity and bioavailability. To evaluate the binding of the newly formed complex with DNA (which results in halting the cell cycle) or serum albumin protein (drug transporter to the tissues), in-silico molecular modeling was employed. Experimental results (spectroscopic and non-spectroscopic) showed that the new compound interacts with each biomolecule via hydrogen bond and van der Waals interactions. Molecular docking demonstrated the binding of this complex to the DNA groove and site I of BSA occurs mainly through hydrogen bonds. Molecular dynamics simulation confirmed the interactions between [Pd (phen)(SSA)] with DNA or BSA through stable hydrogen bonds.

Phenanthroline and phenyl carboxylate mixed ligand copper complexes in developing drugs to treat cancer.

The success of a classic inorganic coordination compound, Cisplatin, cis-[Pt(NH3)2Cl2], as the first anticancer metallodrug started a field of research dedicated to discovering coordination compounds with antitumor activity, encompassing various metals. Among these, copper complexes have emerged as interesting candidates to develop drugs to treat cancer. In this work, mixed ligand complexes of Cu(II) with diimines (phenanthroline or 4-methylphenanthroline) and 3-(4-hydroxyphenyl)propanoate, phenylcarboxylate or phenylacetate were synthesized. They were characterized in the solid state, including a new crystal structure of [Cu2(3-(4-hydroxyphenyl)propanoate)3(phenanthroline)2]Cl·H2O. The obtained complexes presented a variety of stoichiometries. In solution, complexes were partially dissociated in the corresponding Cu-diimine complex. The complexes bound to the DNA by partial intercalation and groove binding, as assessed by Circular Dichroism, relative viscosity change and UV-Vis titration. The cytotoxicity of the complexes was determined in vitro on MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (breast nontumoral), A549 (human lung epithelial carcinoma), and MRC-5 (human nontumoral lung epithelial cells), finding an activity higher than that of Cisplatin, although with less selectivity.

Studies of Anticancer Activities In Vitro and In Vivo for Butyltin(IV)-Iridium(III) Imidazole-Phenanthroline Complexes with Aggregation-Induced Emission Properties.

Organotin(IV) and iridium(III) complexes have shown good application potential in the field of anticancer; however, the aggregation-caused quenching (ACQ) effect induced by high concentration or dose has limited the research on their targeting and anticancer mechanism. Then, a series of aggregation-induced emission (AIE)-activated butyltin(IV)-iridium(III) imidazole-phenanthroline complexes were prepared in this study. Complexes exhibited significant fluorescence improvement in the aggregated state because of the restricted intramolecular rotation (RIR), accompanied by an absolute fluorescence quantum yield of up to 29.2% (IrSn9). Complexes demonstrated potential in vitro antiproliferative and antimigration activity against A549 cells, following a lysosomal-mitochondrial apoptotic pathway. Nude mouse models further confirmed that complexes had favorable in vivo antitumor and antimigration activity in comparison to cisplatin. Therefore, butyltin(IV)-iridium(III) imidazole-phenanthroline complexes possess the potential as potential substitutes for platinum-based drugs.

A new colorimetric lactate biosensor based on CUPRAC reagent using binary enzyme (lactate-pyruvate oxidases)-immobilized silanized magnetite nanoparticles.

A novel optical lactate biosensor is presented that utilizes a colorimetric interaction between H2O2 liberated by a binary enzymatic reaction and bis(neocuproine)copper(II) complex ([Cu(Nc)2]2+) known as CUPRAC (cupric reducing antioxidant capacity) reagent. In the first step, lactate oxidase (LOx) and pyruvate oxidase (POx) were separately immobilized on silanized magnetite nanoparticles (SiO2@Fe3O4 NPs), and thus, 2 mol of H2O2 was released per 1 mol of the substrate due to a sequential enzymatic reaction of the mixture of LOx-SiO2@Fe3O4 and POx-SiO2@Fe3O4 NPs with lactate and pyruvate, respectively. In the second step, the absorbance at 450 nm of the yellow-orange [Cu(Nc)2]+ complex formed through the color reaction of enzymatically produced H2O2 with [Cu(Nc)2]2+ was recorded. The results indicate that the developed colorimetric binary enzymatic biosensor exhibits a broad linear range of response between 0.5 and 50.0 µM for lactate under optimal conditions with a detection limit of 0.17 µM. The fabricated biosensor did not respond to other saccharides, while the positive interferences of certain reducing compounds such as dopamine, ascorbic acid, and uric acid were minimized through their oxidative removal with a pre-oxidant (NaBiO3) before enzymatic and colorimetric reactions. The fabricated optical biosensor was applied to various samples such as artificial blood, artificial/real sweat, and cow milk. The high recovery values (close to 100%) achieved for lactate-spiked samples indicate an acceptable accuracy of this colorimetric biosensor in the determination of lactate in real samples. Due to the increase in H2O2 production with the bienzymatic lactate sensor, the proposed method displays double-fold sensitivity relative to monoenzymatic biosensors and involves a neat color reaction with cupric-neocuproine having a clear stoichiometry as opposed to the rather indefinite stoichiometry of analogous redox dye methods.

Direct and Sensitive Electrochemical Determination of Total Antioxidant Capacity in Foods Using Nanochannel-Based Enrichment of Redox Probes.

Simple and sensitive determination of total antioxidant capacity (TAC) in food samples is highly desirable. In this work, an electrochemical platform was established based on a silica nanochannel film (SNF)-modified electrode, facilitating fast and highly sensitive analysis of TAC in colored food samples. SNF was grown on low-cost and readily available tin indium oxide (ITO) electrode. Fe3+-phenanthroline complex-Fe(III)(phen)3 was applied as the probe, and underwent chemical reduction to form Fe2+-phenanthroline complex-Fe(II)(phen)3 in the presence of antioxidants. Utilizing an oxidative voltage of +1 V, chronoamperometry was employed to measure the current generated by the electrochemical oxidation of Fe(II)(phen)3, allowing for the assessment of antioxidants. As the negatively charged SNF displayed remarkable enrichment towards positively charged Fe(II)(phen)3, the sensitivity of detection can be significantly improved. When Trolox was employed as the standard antioxidant, the electrochemical sensor demonstrated a linear detection range from 0.01 µM to 1 µM and from 1 µM to 1000 µM, with a limit of detection (LOD) of 3.9 nM. The detection performance is better that that of the conventional colorimetric method with a linear de range from 1 µM to 40 µM. Owing to the anti-interfering ability of nanochannels, direct determination of TAC in colored samples including coffee, tea, and edible oils was realized.

The impact of biomolecule interactions on the cytotoxic effects of rhenium(I) tricarbonyl complexes.

Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)3(NN)(py)+ core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes fac-[Re(CO)3(NN)(py)]+, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) or dipyrido[3,2-a:2'3'-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that fac-[Re(CO)3(dppz)(py)]+ has higher Log Po/w and binding constant (Kb) with biomolecules (protein, lipid and DNA) compared to complexes of fac-[Re(CO)3(phen)(py)]+ and fac-[Re(CO)3(dpq)(py)]+. As consequence, fac-[Re(CO)3(dppz)(py)]+ exhibited the highest cytotoxicity (IC50 = 8.5 µM for HeLa cells) for fac-[Re(CO)3(dppz)(py)]+ among the studied compounds (IC50 > 15 µM). This highest cytotoxicity of fac-[Re(CO)3(dppz)(py)]+ are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).

Design and anticancer behaviour of cationic/neutral half-sandwich iridium(III) imidazole-phenanthroline/phenanthrene complexes.

Considerable attention has been devoted to the exploration of organometallic iridium(III) (IrIII) complexes for their potential as metallic anticancer drugs. In this study, twelve half-sandwich IrIII imidazole-phenanthroline/phenanthrene complexes were prepared and characterized. Complexes exhibited promising in-vitro anti-proliferative activity, and some are obviously superior to cisplatin towards A549 cells. These complexes possessed suitable fluorescence, and a non-energy-dependent uptake pathway was identified, subsequently leading to their accumulation in the lysosome and the lysosomal damage. Additionally, complexes could inhibit the cell cycle (G1-phase) and catalyze intracellular NADH oxidation, thus substantiating the elevation of intracellular reactive oxygen species (ROS) level, which confirming the oxidative mechanism. Western blotting further confirmed that complexes could induce A549 cell apoptosis through the lysosomal-mitochondrial anticancer pathway, which was inconsistent with cisplatin. In summary, these complexes offer fresh concepts for the development of organometallic non­platinum anticancer drugs.

Synthesis, Characterization, and Cytotoxicity Evaluation of Novel Water-Soluble Cationic Platinum(II) Organometallic Complexes with Phenanthroline and Imidazolic Ligands.

Platinum-based chemotherapeutic agents are widely used in the treatment of cancer. However, their effectiveness is limited by severe adverse reactions, drug resistance, and poor water solubility. This study focuses on the synthesis and characterization of new water-soluble cationic monofunctional platinum(II) complexes starting from the [PtCl(η1-C2H4OEt)(phen)] (1, phen=1,10-phenanthroline) precursor, specifically [Pt(NH3)(η1-C2H4OEt)(phen)]Cl (2), [Pt(1-hexyl-1H-imidazole)(η1-C2H4OEt)(phen)]Cl (3), and [Pt(1-hexyl-1H-benzo[d]imidazole)(η1-C2H4OEt)(phen)]Cl (4), which deviate from traditional requirements for antitumor activity. These complexes were evaluated for their cytotoxic effects in comparison to cisplatin, using immortalized cervical adenocarcinoma cells (HeLa), human renal carcinoma cells (Caki-1), and normal human renal cells (HK-2). While complex 2 showed minimal effects on the cell lines, complexes 3 and 4 demonstrated higher cytotoxicity than cisplatin. Notably, complex 4 displayed the highest cytotoxicity in both cancer and normal cell lines. However, complex 3 exhibited the highest selectivity for renal tumor cells (Caki-1) among the tested complexes, compared to healthy cells (HK-2). This resulted in a significantly higher selectivity than that of cisplatin and complex 4. Therefore, complex 3 shows potential as a leading candidate for the development of a new generation of platinum-based anticancer drugs, utilizing biocompatible imidazole ligands while demonstrating promising anticancer properties.

2-Aryl-1H-imidazo[4,5-f][1,10]phenanthroline-Based Binuclear Ru(II)/Ir(III)/Re(I) Complexes as Mitochondria Targeting Cancer Stem Cell Therapeutic Agents.

A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [Ru2L1, Ru2L2, Ir2L1, Ir2L2, Re2L1, and Re2L2] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex Ru2L1 and Ir2L2 are two proficient complexes among all, but Ru2L1 is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕf) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in Ru2L1-treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in Ir2L2-treated cells, which correlated with autophagy reticence.

Evaluation of 1,10-phenanthroline-based hydroxamate derivative as dual histone deacetylases/ribonucleotide reductase inhibitor with antitumor activities.

BACKGROUND: Aberrant expression of histone deacetylases (HDACs) and ribonucleotide reductase (RR) enzymes are commonly observed in various cancers. Researchers are focusing on these enzymes in cancer studies with the aim of developing effective chemotherapeutic drugs for cancer treatment. Targeting both HDAC and RR simultaneously with a dual HDAC/RR inhibitor has exhibited enhanced effectiveness compared to monotherapy in cancer treatment, making it a promising strategy. OBJECTIVES: The objective of the study is to synthesize and assess the anti-cancer properties of a 1,10-phenanthroline-based hydroxamate derivative, characterizing it as a novel dual HDAC/RR inhibitor. METHODS: The N1-hydroxy-N8-(1,10-phenanthrolin-5-yl)octanediamide (PA), a 1,10-phenanthroline-based hydroxamate derivative, was synthesized and structurally characterized. The compound was subjected to in vitro assessments of its anti-cancer, HDAC, and RR inhibitory activities. In silico docking and molecular dynamics simulations were further studied to explore its interactions with HDACs and RRM2. RESULTS: The structurally confirmed PA exhibited antiproliferative activity in SiHa cells with an IC50 of 16.43 µM. It displayed potent inhibitory activity against HDAC and RR with IC50 values of 10.80 µM and 9.34 µM, respectively. Co-inhibition of HDAC and RR resulted in apoptosis-induced cell death in SiHa cells, mediated by the accumulation of reactive oxygen species (ROS). In silico docking studies demonstrated that PA can effectively bind to the active sites of HDAC isoforms and RRM2. Furthermore, PA demonstrated a more favorable interaction with HDAC7, displaying a docking score of -9.633 kcal/mol, as compared to the standard HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), which exhibited a docking score of -8.244 kcal/mol against HDAC7. CONCLUSION: The present study emphasizes the prospect of designing a potential 1,10-phenanthroline hydroxamic acid derivative as a novel dual HDAC and RR-inhibiting anti-cancer molecule.

Comparative Study of Sonodynamic and Photoactivated Cancer Therapies with Re(I)-Tricarbonyl Complexes Comprising Phenanthroline Ligands.

Herein, we have compared the effectivity of light-based photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1-Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1-Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark- or light- or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1O2 and OH• on light/ultrasound exposure. Moreover, Re3 induced NADH photo-oxidation in PBS and produced H2O2. To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.

Arene-Arene Coupled Disulfamethazines (or Sulfadiazine)-Phenanthroline-Metal(II) Complexes were Synthesized by In Situ Reactions and Inhibited the Growth and Development of Triple-Negative Breast Cancer through the Synergistic Effect of Antiangiogenesis, Anti-Inflammation, Pro-Apoptosis, and Cuproptosis.

The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development. The molecular mechanism was confirmed that HA-Cu could downregulate the expression of key proteins in the VEGF/VEGFR2 signaling pathway and the expression of inflammatory cytokines, enhance the advantage of pro-apoptotic protein Bax, and enforce cuproptosis by weakening the expression of FDX1 and enhancing the expression of HSP70. Our research will provide a theoretical and practical reference for the development of metal-sulfamethazine and its derivatives as chemotherapy drugs for cancer treatment.

Phenanthroline-functionalized donor-acceptor covalent organic frameworks as photo-responsive nanozymes for visual colorimetric detection of isoniazid.

Development of metal-free nanozymes has raised concern for their extensive applications in photocatalysis and sensing fields. As novel metal-free nanomaterials, covalent organic frameworks (COFs) have engendered intense interest in the construction of nanozymes due to their structural controllability and molecular functionality. The formation of the molecular arrangement by embedding orderly donor-acceptors (D-A) linked in the framework topology to modulate material properties for highly efficient enzyme mimicking activity is of importance but challenging. Here, a strong D-A type of COF was designed and synthesized by integrating electron donor units (pyrene) and electron acceptor units (phenanthroline), named Py-PD COF. Using experiments and theoretical calculations, the introduction of a phenanthroline ring endowed the Py-PD COF with a narrowed band gap, and efficient charge transfer and separation. Further, the Py-PD COF exhibited a superior light-responsive oxidase-mimicking characteristic under visible light irradiation, which could catalyze the oxidation of 3,3',5,5-tetramethylbenzidine (TMB) and give the corresponding evolution of color. The nanoenzymatic activity of the Py-PD COF was light-regulated, which offers a fascinating advantage because of its high efficiency and spatial controllability. Based on previously mentioned characteristics, an "on-off" sensing platform for the colorimetric analysis of isoniazid (INH) could be constructed with a good linear relationship (2-100 µM) and a low limit of detection (1.26 µM). This research shows that not only is Py-PD COF an environmentally friendly compound for the colorimetric detection of INH, but it is also capable of providing the interesting D-A type COF-based material for designing an excellent nanozyme.

The copper (II) complex of salicylate phenanthroline induces immunogenic cell death of colorectal cancer cells through inducing endoplasmic reticulum stress.

BACKGROUND: In our previous study, Cu(sal)phen was found to have anti-tumor effects, yet its precise mechanism remains unknown. Research has shown that dying tumor cells release damage-associated molecular patterns (DAMPs) to promote anti-tumor immune response. Therefore, we have further explored the effects and potential molecular mechanisms of Cu(sal)phen-induced immunogenic cell death (ICD) in colorectal cancer (CRC). METHODS: ELISA and flow cytometry were used to detect the effects of Cu(sal)phen treatment on ICD markers. The molecular mechanisms of Cu(sal)phen-induced ICD were investigated through the detection of endoplasmic reticulum stress (ERS) and reactive oxygen species (ROS) in vitro using Western blot and flow cytometry. Additionally, a mouse model was constructed to study the effects of Cu(sal)phen on immune cells and anti-tumor-related cytokines in vivo. RESULTS: Cu(sal)phen induced the release of calreticulin (CRT), adenosine triphosphate (ATP) and high mobility group box 1 (HMGB1), the main molecular markers of ICD, by promoting the accumulation of ROS and inducing ERS. Furthermore, Cu(sal)phen promoted the maturation of dendritic cells (DCs) and activation of CD8+T cells, as well as the secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ), while downregulating transforming growth factor-ß (TGF-ß) levels, thereby activating the anti-tumor immune response. CONCLUSION: Cu(sal)phen has the potential to induce ICD in tumors and activate the adaptive immune response to achieve anti-tumor effects. This makes Cu(sal)phen a promising candidate for the treatment of CRC.

Dissolving Microneedle-Based Cascade-Activation Nanoplatform for Enhanced Photodynamic Therapy of Skin Cancer.

Purpose: Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ). Methods: TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar. Chlorin e6 (Ce6) was loaded in DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6 (DPTC). To further improve tumor infiltration and accumulation, hyaluronic acid was adopted to make DPTC-containing microneedles (DPTC-MNs). Results: Both in vitro and in vivo studies consistently demonstrated the synergistic antitumor effect of photodynamic therapy and TPZ achieved by DPTC-MNs. With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process. Conclusion: The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.