Co-crosslinking strategy for dual functionalization of small magnetic nanoparticles with redox probes and biological probes.

Surface functionalization strategy is becoming a crucial bridge from magnetic nanoparticles (MNPs) to their broad bio-application. To realize the multiple functions of MNPs such as magnetic manipulation, target capture, and signal amplification in their use of electrochemical biosensing, co-crosslinking strategy was proposed here to construct dual-functionalized MNPs by combining ultra-sensitive redox moieties and specific biological probes. In this work, MNPs with a TEM size of 10 nm were synthesized by co-precipitation for amination and PEGylation to maintain colloid stability once dispersed in high-ionic-strength buffer (such as phosphate-buffered saline). Then, MNPs@IgG were prepared via the bis(sulfosuccinimidyl) suberate (BS3) cross-linker to conjugate these IgG onto the MNP surface, with a binding efficiency of 73%. To construct dual-functionalized MNPs, these redox probes of ferrocene-NHS (Fc) were co-crosslinked onto the MNP surface, together with IgG, by using BS3. The developed MNPs@Redox@IgG were characterized by SDS‒PAGE to identify IgG binding and by square wave voltammetry (SWV) to validate the redox signal. Additionally, the anti-CD63 antibodies were selected for the development of MNPs@anti-CD63 for use in the bio-testing of exosome sample capture. Therefore, co-crosslinking strategy paved a way to develop dual-functionalized MNPs that can be an aid of their potential utilization in diagnostic assay or electrochemical methods.

Hybrid nanoflower-based electrochemical lateral flow immunoassay for Escherichia coli O157 detection.

An electrochemical biosensor has been developed for detection of Escherichia coli O157 by integrating lateral flow with screen-printed electrodes. The screen-printed electrodes were attached under the lateral flow detection line, and organic-inorganic nanoflowers prepared from E. coli O157-specific antibodies as an organic component were attached to the lateral flow detection line. In the presence of E. coli O157, an organic-inorganic nanoflower-E. coli O157-antimicrobial peptide-labelled ferrocene sandwich structure is formed on the lateral flow detection line. Differential pulse voltammetry is applied using a smartphone-based device to monitor ferrocene on the detection line. The resulting electrochemical biosensor could specifically detect E. coli O157 with a limit of detection of 25 colony-forming units mL-1. Through substitution of antibodies of organic components in organic-inorganic nanoflowers, biosensors have great potential for the detection of other pathogens in biomedical research and clinical diagnosis.

Improvement of in vivo iron bioavailability using mung bean peptide-ferrous chelate.

There is an increasing amount of research into the development of a third generation of iron supplementation using peptide-iron chelates. Peptides isolated from mung bean were chelated with ferrous iron (MBP-Fe) and tested as a supplement in mice suffering from iron-deficiency anemia (IDA). Mice were randomly divided into seven groups: a group fed the normal diet, the IDA model group, and IDA groups treated with inorganic iron (FeSO4), organic iron (ferrous bisglycinate, Gly-Fe), low-dose MBP-Fe(L-MBP-Fe), high-dose MBP-Fe(H-MBP-Fe), and MBP mixed with FeSO4 (MBP/Fe). The different iron supplements were fed for 28 days via intragastric administration. The results showed that MBP-Fe and MBP/Fe had ameliorative effects, restoring hemoglobin (HGB), red blood cell (RBC), hematocrit (HCT), and serum iron (SI) levels as well as total iron binding capacity (TIBC) and body weight gain of the IDA mice to normal levels. Compared to the inorganic (FeSO4) and organic (Gly-Fe) iron treatments, the spleen coefficient and damage to liver and spleen tissues were significantly lower in the H-MBP-Fe and MBP/Fe mixture groups, with reparative effects on jejunal tissue. Gene expression analysis of the iron transporters Dmt 1 (Divalent metal transporter 1), Fpn 1 (Ferroportin 1), and Dcytb (Duodenal cytochrome b) indicated that MBP promoted iron uptake. These findings suggest that mung bean peptide-ferrous chelate has potential as a peptide-based dietary supplement for treating iron deficiency.

Digestion and absorption characteristics of iron-chelating silver carp scale collagen peptide and insights into their chelation mechanism.

Iron deficiency is widespread throughout the world, supplementing sufficient iron or improving the bioavailability of iron is the fundamental strategy to solve the problem of iron scarcity. Herein, we explored a new form of iron supplement, iron chelates of silver carp scales (SCSCP-Fe) were prepared from collagen peptide of silver carp scales (SCSCP) and FeCl2·4H2O, the effects of external environment and simulated gastrointestinal digestive environment on the stability of SCSCP-Fe and the structural changes of peptide iron chelates during digestion were investigated. The results of in vitro iron absorption promotion showed that the iron bioavailability of SCSCP-Fe was higher than that of FeSO4. Two potential high iron chelating peptides DTSGGYDEY (DY) and LQGSNEIEIR (LR) were screened and synthesized from the SCSCP sequence by molecular dynamics and LC-MS/MS techniques. The FTIR results displayed that the binding sites of DY and LR for Fe2+ were the carboxyl group, the amino group, and the nitrogen atom on the amide group on the peptide. ITC results indicated that the chelation reactions of DY and LR with Fe2+ were mainly dominated by electrostatic interactions, forming chelates in stoichiometric ratios of 1:2 and 1:1, respectively. Both DY and LR had a certain ability to promote iron absorption. The transport of DY-Fe chelate may be a combination of the three pathways: PepT1 vector pathway, cell bypass, and endocytosis, while LR-Fe chelate was dominated by bivalent metal ion transporters. This study is expected to provide theoretical reference and technical support for the high-value utilization of silver carp scales and the development of novel iron supplements.

Construction of Metal-Organic Framework as a Novel Platform for Ratiometric Determination of Cyanide.

Metal-organic frameworks (MOFs) are frequently utilized as sensing materials. Unfortunately, the low conductivity of MOFs hinder their further application in electrochemical determination. To overcome this limitation, a novel modification strategy for MOFs was proposed, establishing an electrochemical determination method for cyanides in Baijiu. Co and Ni were synergistically used as the metal active centers, with meso-Tetra(4-carboxyphenyl)porphine (TCPP) and Ferrocenecarboxylic acid (Fc-COOH) serving as the main ligands, synthesizing Ni/Co-MOF-TCPP-Fc through a hydrothermal method. The prepared MOF exhibited improved conductivity and stable ratio signals, enabling rapid and sensitive determination of cyanides. The screen-printed carbon electrodes (SPCE) were suitable for in situ and real-time determination of cyanide by electrochemical sensors due to their portability, low cost, and ease of mass production. A logarithmic linear response in the range of 0.196~44 ng/mL was demonstrated by this method, and the limit of detection (LOD) was 0.052 ng/mL. Compared with other methods, the sensor was constructed by a one-step synthesis method, which greatly simplifies the analysis process, and the determination time required was only 4 min. During natural cyanide determinations, recommended readouts match well with GC-MS with less than 5.9% relative error. Moreover, this electrochemical sensor presented a promising method for assessing the safety of cyanides in Baijiu.

A Study on the Mechanism and Properties of a Self-Powered H2O2 Electrochemical Sensor Based on a Fuel Cell Configuration with FePc and Graphene Cathode Catalyst Materials.

Conventional electrochemical sensors use voltammetric and amperometric methods with external power supply and modulation systems, which hinder the flexibility and application of the sensors. To avoid the use of an external power system and to minimize the number of electrochemical cell components, a self-powered electrochemical sensor (SPES) for hydrogen peroxide was investigated here. Iron phthalocyanine, an enzyme mimetic material, and Ni were used as a cathode catalyst and an anode material, respectively. The properties of the iron phthalocyanine catalyst modified by graphene nanoplatelets (GNPs) were investigated. Open circuit potential tests demonstrated the feasibility of this system. The GNP-modulated interface helped to solve the problems of aggregation and poor conductivity of iron phthalocyanine and allowed for the achievement of the best analytical characteristics of the self-powered H2O2 sensor with a low detection limit of 0.6 µM and significantly higher sensitivity of 0.198 A/(M·cm2) due to the enhanced electrochemical properties. The SPES demonstrated the best performance at pH 3.0 compared to pH 7.4 and 12.0. The sensor characteristics under the control of external variable load resistances are discussed and the cell showed the highest power density of 65.9 µW/cm2 with a 20 kOhm resistor. The practical applicability of this method was verified by the determination of H2O2 in blood serum.

Harnessing Redox Polymer Dynamics for Enhanced Glucose-Oxygen Coupling in Dual Biosensing and Therapeutic Applications.

The burgeoning field of continuous glucose monitoring (CGM) for diabetes management faces significant challenges, particularly in achieving precise and stable biosensor performance under changing environmental conditions such as varying glucose concentrations and O2 levels. To address this, we present a novel biosensor based on the electroless coupling of glucose oxidation catalyzed by flavin-dependent glucose dehydrogenase (FAD-GDH) and O2 reduction catalyzed by bilirubin oxidase (BOD) via a redox polymer, dimethylferrocene-modified linear poly(ethylenimine), FcMe2-LPEI. Initial cyclic voltammetry tests confirm the colocalization of both enzymatic reactions within the potential range of the polymer, indicating an effective electron shuttle mechanism. As a result, we created a hybrid biosensor that operates at open-circuit potential (OCP). It can detect glucose concentrations of up to 100 mM under various O2 conditions, including ambient air. This resulted from optimizing the enzyme ratio to 120 ± 10 mUBOD·UFAD-GDH-1·atmO2-1. This biosensor is highly sensitive, a crucial feature for CGM applications. This distinguishes it from FAD-GDH traditional biosensors, which require a potential to be applied to measure glucose concentrations up to 30 mM. In addition, this biosensor demonstrates the ability to function as a noninvasive, external device that can adapt to changing glucose levels, paving the way for its use in diabetes care and, potentially, personalized healthcare devices. Furthermore, by leveraging the altered metabolic pathways in tumor cells, this system architecture opened up new avenues for targeted glucose scavenging and O2 reduction in cancer therapy.

Deciphering the Catalytic Mechanism of Peroxidase-like Activity of Iron Sulfide Nanozymes.

Iron sulfide nanomaterials represented by FeS2 and Fe3S4 nanozymes have attracted increasing attention due to their biocompatibility and peroxidase-like (POD-like) catalytic activity in disease diagnosis and treatments. However, the mechanism responsible for their POD-like activities remains unclear. Herein, taking the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) by H2O2 on FeS2(100) and Fe3S4(001) surfaces, the catalytic mechanism was investigated in detail using density functional theory (DFT) calculations and experimental characterizations. Our experimental results showed that the catalytic activity of FeS2 nanozymes was significantly higher than that of Fe3S4 nanozymes. Our DFT calculations indicated that the surface iron ions of iron sulfide nanozymes could effectively catalyze the production of HO• radicals via the interactions between Fe 3d electrons and the frontier orbitals of H2O2 in the range of -10 to 5 eV. However, FeS2 nanozymes exhibited higher POD-like activity due to the surface Fe(II) binding to H2O2, forming inner-orbital complexes, which results in a larger binding energy and a smaller energy barrier for the base-like decomposition of H2O2. In contrast, the surface iron ions of Fe3S4 nanozymes bind to H2O2, forming outer-orbital complexes, which results in a smaller binding energy and a larger energy barrier for the base-like decomposition of H2O2. The charge transfer analysis showed that FeS2 nanozymes transferred 0.12 e and Fe3S4 nanozymes transferred 0.05 e from their surface iron ions to H2O2, respectively. The simulations were consistent with the experimental observations that the FeS2 nanozymes had a greater affinity for H2O2 compared to that of Fe3S4 nanozymes. This work provides a theoretical foundation for the rational design and accurate preparation of iron sulfide functional nanozymes.

A novel dual-signal output strategy for POCT of CEA based on a smartphone electrochemical aptasensing platform.

A smartphone-based electrochemical aptasensing platform was developed for the point-of-care testing (POCT) of carcinoembryonic antigen (CEA) based on the ferrocene (Fc) and PdPt@PCN-224 dual-signal labeled strategy. The prepared PdPt@PCN-224 nanocomposite showed a strong catalytic property for the reduction of H2O2. Phosphate group-labeled aptamer could capture PdPt@PCN-224 by Zr-O-P bonds to form PdPt@PCN-224-P-Apt. Therefore, a dual signal labeled probe was formed by the hybridization between Fc-DNA and PdPt@PCN-224-P-Apt. The presence of CEA forced PdPt@PCN-224-P-Apt to leave the electrode surface due to the specific affinity, leading to the decrease of the reduction current of H2O2. At the same time, the Fc-DNA strand changed to hairpin structure, which made Fc closer to the electrode and resulted in the increase of the oxidation current of Fc. Thus, CEA can be accurately determined through both signals: the decrease of H2O2 reduction current and the increase of Fc oxidation current, which could avoid the false positive signal. Under the optimal conditions, the prepared aptasensor exhibited a wide linear range from 1 pg·mL-1 to 100 ng·mL-1 and low detection limits of 0.98 pg·mL-1 and 0.27 pg·mL-1 with Fc and PdPt@PCN-224 as signal labels, respectively. The aptasensor developed in this study has successfully demonstrated its capability to detect CEA in real human serum samples. These findings suggest that the proposed sensing platform will hold great potential for clinical tumor diagnosis and monitoring.

Multifunctional Organometallic Compounds Active against Infective Trypanosomes: Ru(II) Ferrocenyl Derivatives with Two Different Bioactive Ligands.

Human African trypanosomiasis (HAT, sleeping sickness) and American trypanosomiasis (Chagas disease) are endemic zoonotic diseases caused by genomically related trypanosomatid protozoan parasites (Trypanosoma brucei and Trypanosoma cruzi, respectively). Just a few old drugs are available for their treatment, with most of them sharing poor safety, efficacy, and pharmacokinetic profiles. Only fexinidazole has been recently incorporated into the arsenal for the treatment of HAT. In this work, new multifunctional Ru(II) ferrocenyl compounds were rationally designed as potential agents against these pathogens by including in a single molecule 1,1'-bis(diphenylphosphino)ferrocene (dppf) and two bioactive bidentate ligands: pyridine-2-thiolato-1-oxide ligand (mpo) and polypyridyl ligands (NN). Three [Ru(mpo)(dppf)(NN)](PF6) compounds and their derivatives with chloride as a counterion were synthesized and fully characterized in solid state and solution. They showed in vitro activity on bloodstream T. brucei (EC50 = 31-160 nM) and on T. cruzi trypomastigotes (EC50 = 190-410 nM). Compounds showed the lowest EC50 values on T. brucei when compared to the whole set of metal-based compounds previously developed by us. In addition, several of the Ru compounds showed good selectivity toward the parasites, particularly against the highly proliferative bloodstream form of T. brucei. Interaction with DNA and generation of reactive oxygen species (ROS) were ruled out as potential targets and modes of action of the Ru compounds. Biochemical assays and in silico analysis led to the insight that they are able to inhibit the NADH-dependent fumarate reductase from T. cruzi. One representative hit induced a mild oxidation of low molecular weight thiols in T. brucei. The compounds were stable for at least 72 h in two different media and more lipophilic than both bioactive ligands, mpo and NN. An initial assessment of the therapeutic efficacy of one of the most potent and selective candidates, [Ru(mpo)(dppf)(bipy)]Cl, was performed using a murine infection model of acute African trypanosomiasis. This hit compound lacks acute toxicity when applied to animals in the dose/regimen described, but was unable to control parasite proliferation in vivo, probably because of its rapid clearance or low biodistribution in the extracellular fluids. Future studies should investigate the pharmacokinetics of this compound in vivo and involve further research to gain deeper insight into the mechanism of action of the compounds.

High-Frequency Quartz Crystal Microbalance and Dual-Signaling Electrochemical Ratiometric Assays of PTP1B Activity Based on COF@Au@Fc Hybrids.

The abnormal expression of protein tyrosine phosphatase 1B (PTP1B) is highly related to several serious human diseases. Therefore, an accurate PTP1B activity assay is beneficial to the diagnosis and treatment of these diseases. In this study, a dual-mode biosensing platform that enabled the sensitive and accurate assay of PTP1B activity was constructed based on the high-frequency (100 MHz) quartz crystal microbalance (QCM) and dual-signaling electrochemical (EC) ratiometric strategy. Covalent-organic framework@gold nanoparticles@ferrocene@single-strand DNA (COF@Au@Fc-S0) was introduced onto the QCM Au chip via the chelation between Zr4+ and phosphate groups (phosphate group of the phosphopeptide (P-peptide) on the QCM Au chip and the phosphate group of thiol-labeled single-stranded DNA (S0) on COF@Au@Fc-S0) and used as a signal reporter. When PTP1B was present, the dephosphorylation of the P-peptide led to the release of COF@Au@Fc-S0 from the QCM Au chip, resulting in an increase in the frequency of the QCM. Meanwhile, the released COF@Au@Fc-S0 hybridized with thiol/methylene blue (MB)-labeled hairpin DNA (S1-MB) on the Au NPs-modified indium-tin oxide (ITO) electrode. This caused MB to be far away from the electrode surface and Fc to be close to the electrode, leading to a decrease in the oxidation peak current of MB and an increase in the oxidation peak current of Fc. Thus, PTP1B-induced dephosphorylation of the P-peptide was monitored in real time by QCM, and PTP1B activity was detected sensitively and reliably using this innovative QCM-EC dual-mode sensing platform with an ultralow detection limit. This platform is anticipated to serve as a robust tool for the analysis of protein phosphatase activity and the discovery of drugs targeting protein phosphatase.

Highly catalytic sulfur-doped and bimetal-coordinated CoFe(CN)5NO nanoparticles coupled with PER/HCR amplification cascades for sensitive electrochemical aptamer luteinizing hormone assay.

Sensitive monitoring of luteinizing hormone (LH), a glycoprotein that regulates the synthesis of regulatory steroid hormones, can facilitate the diagnosis of various reproductive diseases. In this work, a new and highly catalytic Sulfur-doped and bimetal-coordinated CoFe(CN)5NO (denoted as S-CoFe(CN)5NO) nanoparticles are synthesized. Such material is further used to construct high performance sensing interface and coupled with primer exchange reaction (PER) and hybridization chain reaction (HCR) amplification cascades for sensitive electrochemical aptamer-based LH assay. Target LH molecules bind aptamer sequences in DNA duplex probes to liberate ssDNA strands, which initiate subsequent PER/HCR amplification cascades for the capture of many ferrocene (Fc)-tagged DNAs on sensing interface. S-CoFe(CN)5NO subsequently leads to catalytic oxidation of these Fc tags for yielding substantially magnified currents for realizing ultrasensitive assay of LH with the detection limit of 0.69 pM in range from 5 pM to 10 nM. Owing to the high specificity of aptamer, such sensor has high selectivity and can achieve low levels of LH assay in diluted serum samples. With the successful demonstration for detecting trace LH, such sensor can be easily extended as a universal aptamer-based electrochemical sensing method for monitoring various target analytes in the biomedical and biological fields.

Grinding siderite with ferric sulfate to generate an active ferrous source for Cr(VI) reduction.

Activated siderite, endowed with excellent properties, was simply prepared by co-grinding with Fe sulfate to enhance its high reducing ability for Cr(VI). Batch experiments were conducted to investigate the main affecting parameters, such as material ratio, pH, temperature, etc. The removal of Cr(VI) by activated siderite was completed within 4 h of the reaction. The activated siderite maintained a high removal effect of Cr(VI) within a wide pH range (3-9). Various analytical methods, including XRD, SEM/EDS, XPS, etc., were employed to characterize the samples and discover variations before and after the reaction. The Fe (Ⅱ) in activated siderite becomes highly active, and it can even be released from the solid phase in the mildly acidic liquid phase to efficiently reduce Cr(VI) and mitigate its toxicity. These findings introduce an innovative approach for activating various minerals widely distributed in nature to promote the recovery of the ecological system.

A microfluidic ratiometric electrochemical aptasensor for highly sensitive and selective detection of 3,3',4,4'-tetrachlorobiphenyl.

This study proposes a strategy using a microfluidic ratiometric electrochemical aptasensor to detect PCB77 with excellent sensitivity and specificity. This sensing platform combines a microfluidic chip, a wireless integrated circuit system for aptamer-based electrochemical detection, and a mobile phone control terminal for parameter configuration, identification, observation, and wireless data transfer. The sensing method utilizes a cDNA (MB-COOH-cDNA-SH) that is labelled with the redox probe Methylene Blue (MB) at the 5' end and has a thiol group at the 3' end. Additionally, it utilizes a single strand PCB aptamer that has been modified with ferrocenes at the 3' end (aptamer-Fc). Through gold-thiol binding, the labelled probe of MB-COOH-cDNA-SH was self-assembled onto the surface of an Au/Nb2CTx/GO modified electrode. On exposure to aptamer-Fc, it will hybridize with MB-COOH-cDNA-SH to form a stable double-stranded structure on the electrode surface. When PCB77 is present, aptamer-Fc binds specifically to the target, enabling the double-stranded DNA to unwind. Such variation caused changes in the differential pulse voltammetry (DPV) peak currents of both MB and Fc. A substantial improvement is observed in the ratio between the two DPV peaks. Under the optimum experimental conditions, this assay has a response that covers the 0.0001 to 1000 ng mL-1 PCB77 concentration range, and the detection limit is 1.56 × 10-5 ng mL-1. The integration of a ratiometric electrochemical aptasensor with designed microfluidic and integrated devices in this work is an innovative and promising approach that offers an efficient platform for on-site applications.

Novel Insights into Sb(III) Oxidation and Immobilization during Ferrous Iron Oxygenation: The Overlooked Roles of Singlet Oxygen and Fe (oxyhydr)oxides Formation.

Reactive oxygen species (ROS) produced from the oxygenation of reactive Fe(II) species significantly affect the transformation of metalloids such as Sb at anoxic-oxic redox interfaces. However, the main ROS involved in Sb(III) oxidation and Fe (oxyhydr)oxides formation during co-oxidation of Sb(III) and Fe(II) are still poorly understood. Herein, this study comprehensively investigated the Sb(III) oxidation and immobilization process and mechanism during Fe(II) oxygenation. The results indicated that Sb(III) was oxidized to Sb(V) by the ROS produced in the aqueous and solid phases and then immobilized by formed Fe (oxyhydr)oxides via adsorption and coprecipitation. In addition, chemical analysis and extended X-ray absorption fine structure (EXAFS) characterization demonstrated that Sb(V) could be incorporated into the lattice structure of Fe (oxyhydr)oxides via isomorphous substitution, which greatly inhibited the formation of lepidocrocite (γ-FeOOH) and decreased its crystallinity. Notably, goethite (α-FeOOH) formation was favored at pH 6 due to the greater amount of incorporated Sb(V). Moreover, singlet oxygen (1O2) was identified as the dominant ROS responsible for Sb(III) oxidation, followed by surface-adsorbed ·OHads, ·OH, and Fe(IV). Our findings highlight the overlooked roles of 1O2 and Fe (oxyhydr)oxide formation in Sb(III) oxidation and immobilization during Fe(II) oxygenation and shed light on understanding the geochemical cycling of Sb coupled with Fe in redox-fluctuating environments.

Fluorinated 1,7-DO2A-Based Iron(II) Complexes as Sensitive 19F MRI Molecular Probes for Visualizing Renal Dysfunction in Living Mice.

Kidney diseases have become an important global health concern due to their high incidence, inefficient diagnosis, and poor prognosis. Devising direct methods, especially imaging means, to assess renal function is the key for better understanding the mechanisms of various kidney diseases and subsequent development of effective treatment. Herein, we developed a fluorinated ferrous chelate-based sensitive probe, 1,7-DO2A-Fe(II)-F18 (Probe 1), for 19F magnetic resonance imaging (MRI). This highly fluorinated probe (containing 18 chemically equivalent 19F atoms with a fluorine content at 35 wt %) achieves a 15-time enhancement in signal intensity compared with the fluorine-containing ligand alone due to the appropriately regulated 19F relaxation times by the ferrous ion, which significantly increases imaging sensitivity and reduces acquisition time. Owing to its high aqueous solubility, biostability, and biocompatibility, this probe could be rapidly cleared by kidneys, which provides a means for monitoring renal dysfunction via 19F MRI. With this probe, we accomplish in vivo imaging of the impaired renal dysfunction caused by various kidney diseases including acute kidney injury, unilateral ureteral obstruction, and renal fibrosis at different stages. Our study illustrates the promising potential of Probe 1 for in vivo real-time visualization of kidney dysfunction, which is beneficial for the study, diagnosis, and even stratification of different kidney diseases. Furthermore, the design strategy of our probe is inspiring for the development of more high-performance 19F MRI probes for monitoring various biological processes.

Colorimetric Detection of Fentanyl Powder on Surfaces Using a Supramolecular Displacement Assay.

Fentanyl is a potent synthetic opioid with an alarmingly low lethal dosage of 2 mg. The equipment necessary to detect fentanyl in field settings (e.g., hand-held spectrometers) is restricted to highly trained, well-funded, and specialized personnel. Established point-of-need technologies, such as lateral flow immunochromatographic strips, are available; however, they often involve multiple contact-based steps (e.g., collection, mixing) that pose a higher risk to users handling unknown substances. Herein, we developed a colorimetric displacement assay capable of contactless detection of fentanyl in liquid or solid samples. The basis of our assay relies on the presence of fentanyl to displace a redox mediator, ferrocene carboxylic acid, inclusively bound in the cavity of a supramolecular host, CB[7]. The displacement is only possible in the presence of high affinity binding guests, like fentanyl (KA ∼ 106 M-1). The liberated redox guest can then react with indicator reagents that are free in solution, producing either: (i) a distinct blue color to indicate the presence of fentanyl or (ii) a pale blue tint in the absence of fentanyl. We demonstrate rapid and specific detection of fentanyl free base and fentanyl derivatives (e.g., acetyl fentanyl and furanyl fentanyl) against a panel of 9 other common drugs of abuse (e.g., morphine, cocaine, and heroin). Furthermore, we highlight the intended use of this assay by testing grains of fentanyl derivatives on a surface with a drop (i.e., 25 µL) of the assay reagent. We anticipate that this approach can be applied broadly to identify the presence of fentanyl at the point of need.

Visible and Red Light-Triggered Anticancer Profile of a Ferrocene-Re(I)-Tricarbonyl Conjugate: Experimental and Theoretical Studies.

We have red-shifted the light absorbance property of a Re(I)-tricarbonyl complex via distant conjugation of a ferrocene moiety and developed a novel complex ReFctp, [Re(Fctp)(CO)3Cl], where Fctp = 4'-ferrocenyl-2,2':6',2″-terpyridine. ReFctp showed green to red light absorption ability and blue emission, indicating its potential for photodynamic therapy (PDT) application. The conjugation of ferrocene introduced ferrocene-based transitions, which lie at a higher wavelength within the PDT therapeutic window. The time-dependent density functional theory and excited state calculations revealed an efficient intersystem crossing for ReFctp, which is helpful for PDT. ReFctp elicited both PDT type I and type II pathways for reactive oxygen species (ROS) generation and facilitated NADH (1,4-dihydro-nicotinamide adenine dinucleotide) oxidation upon exposure to visible light. Importantly, ReFctp showed effective penetration through the layers of clinically relevant 3D multicellular tumor spheroids and localized primarily in mitochondria (Pearson's correlation coefficient, PCC = 0.65) of A549 cancer cells. ReFctp produced more than 20 times higher phototoxicity (IC50 ∼1.5 µM) by inducing ROS generation and altering mitochondrial membrane potential in A549 cancer cells than the nonferrocene analogue Retp, [Re(CO)3(tp)Cl], where tp = 2,2':6',2″-terpyridine. ReFctp induced apoptotic mode of cell death with a notable photocytotoxicity index (PI, PI = IC50dark/IC50light) and selectivity index (SI, SI = normal cell's IC50dark/cancer cell's IC50light) in the range of 25-33.

Photothermal therapy of xenografted tumor by carbon nanoparticles-Fe(II) complex.

Due to the unique structure, carbon nanomaterials could convert near-infrared (NIR) light into heat efficiently in tumor ablation using photothermal therapy (PTT). However, none of them has been applied in clinical treatment, because they have not been approved for clinical evaluations and the precise temperature control facility is scarce. In this study, we designed a temperature-responsive controller for PTT and used carbon nanoparticles-Fe(II) complex (CNSI-Fe) as photothermal conversion agent (PTA) for PTT of tumor in vitro and in vivo. CNSI-Fe was an innovative drug under the evaluations in clinical trials. CNSI-Fe showed excellent photothermal conversion ability in water to increase the water temperature by 40 °C within 5 min under irradiation of 808 nm laser at 0.5 W/cm2. The temperature was precisely controlled at 52 °C for both in vitro and in vivo tumor inhibition. CNSI-Fe with NIR irradiation showed higher tumor cell inhibition than CNSI. In tumor bearing mice, CNSI-Fe with NIR irradiation achieved an inhibition rate of 84.7 % and 71.4 % of them were completely cured. Mechanistically, CNSI-Fe under NIR irradiation induced the radical generation, oxidative damage and ferroptosis to kill tumor. In addition, CNSI-Fe showed good biosafety during PTT according to hematological, serum biological and histopathological examinations. These results indicated that the combination of chemotherapy and PTT provided higher antitumor efficiency using CNSI-Fe as PTA.

Paclitaxel Overload Supramolecular Oxidative Stress Nanoamplifier with a CDK12 Inhibitor for Enhanced Cancer Therapy.

Combination therapy has emerged as a promising approach for treating tumors, although there is room for improvement. This study introduced a novel strategy that combined the enhancement of apoptosis, ferroptosis, and DNA damage to improve therapeutic outcomes for prostate cancer. Specifically, we have developed a supramolecular oxidative stress nanoamplifier, which was comprised of ß-cyclodextrin, paclitaxel, and ferrocene-poly(ethylene glycol). Paclitaxel within the system disrupted microtubule dynamics, inducing G2/M phase arrest and apoptosis. Concurrently, ferrocene utilized hydrogen peroxide to generate toxic hydroxyl radicals in cells through the Fenton reaction, triggering a cascade of reactive oxygen species expansion, reduction of glutathione levels, lipid peroxidation, and ferroptosis. The increased number of hydroxyl radicals and the inhibitory effect of THZ531 on DNA repair mechanisms exacerbated DNA damage within tumor cells. As expected, the supramolecular nanoparticles demonstrated excellent drug delivery ability to tumor cells or tissues, exhibited favorable biological safety in vivo, and enhanced the killing effect on prostate cancer.