pH-responsive iron-loaded carbonaceous nanoparticles for chemodynamic therapy based on the Fenton reaction.

The Fenton reaction-based chemodynamic therapy is a form of cancer therapy, and its efficacy can be significantly improved by promoting catalytic reactions involving iron ions. A system with high catalytic capacity and low biological toxicity that effectively inhibits tumor progression is required for optimal treatment. In this study, iron-loaded carbonaceous nanoparticles (CNPs@Fe) with Fenton catalytic activity were fabricated and applied for the chemodynamic therapy of cancer. The carbonaceous nanoparticles derived from glucose via a caramelization reaction demonstrated high biocompatibility. Besides, aromatic structures in the carbonaceous nanoparticles helped accelerate electron transfer to enhance the catalytic decomposition of H2O2, resulting in the formation of highly reactive hydroxyl radicals (˙OH). At pH 6.0 (representing weak acidity in the tumor microenvironment), the Fenton catalytic activity of CNPs@Fe in the decomposition of H2O2 was 15.3 times higher than that of Fe2+ and 28.3 times higher than that of Fe3O4via a chromogenic reaction. The reasons for the enhancement were revealed by analyzing the chemical composition of carbonaceous nanoparticles using high-resolution mass spectra. The developed Fenton agent also demonstrated significant therapeutic effectiveness and minimal side effects in in vitro and in vivo anticancer studies. This work proposes a novel approach to promote the generation of reactive oxygen species (ROS) for the chemodynamic therapy of cancer.

A Multifunctional, Highly Biocompatible, and Double-Triggering Caramelized Nanotheranostic System Loaded with Fe3O4 and DOX for Combined Chemo-Photothermal Therapy and Real-Time Magnetic Resonance Imaging Monitoring of Triple Negative Breast Cancer.

Purpose: Owing to lack of specific molecular targets, the current clinical therapeutic strategy for triple negative breast cancer (TNBC) is still limited. In recent years, some nanosystems for malignancy treatment have received considerable attention. In this study, we prepared caramelized nanospheres (CNSs) loaded with doxorubicin (DOX) and Fe3O4 to achieve the synergistic effect of combined therapy and real-time magnetic resonance imaging (MRI) monitoring, so as to improve the diagnosis and therapeutic effect of TNBC. Methods: CNSs with biocompatibility and unique optical properties were prepared by hydrothermal method, DOX and Fe3O4 were loaded on it to obtain Fe3O4/DOX@CNSs nanosystem. Characteristics including morphology, hydrodynamic size, zeta potentials and magnetic properties of Fe3O4/DOX@CNSs were evaluated. The DOX release was evaluated by different pH/near-infrared (NIR) light energy. Biosafety, pharmacokinetics, MRI and therapeutic treatment of Fe3O4@CNSs, DOX and Fe3O4/DOX@CNSs were examined in vitro or in vivo. Results: Fe3O4/DOX@CNSs has an average particle size of 160 nm and a zeta potential of 27.5mV, it demonstrated that Fe3O4/DOX@CNSs is a stable and homogeneous dispersed system. The hemolysis experiment of Fe3O4/DOX@CNSs proved that it can be used in vivo. Fe3O4/DOX@CNSs displayed high photothermal conversion efficiency, extensive pH/heat-induced DOX release. 70.3% DOX release is observed under the 808 nm laser in the pH = 5 PBS solution, obviously higher than pH = 5 (50.9%) and pH = 7.4 (less than 10%). Pharmacokinetic experiments indicated the t1/2ß, and AUC0-t of Fe3O4/DOX@CNSs were 1.96 and 1.31 -fold higher than those of DOX solution, respectively. Additionally, Fe3O4/DOX@CNSs with NIR had the greatest tumor suppression in vitro and in vivo. Moreover, this nanosystem demonstrated distinct contrast enhancement on T2 MRI to achieve real-time imaging monitoring during treatment. Conclusion: Fe3O4/DOX@CNSs is a highly biocompatible, double-triggering and improved DOX bioavailability nanosystem that combines chemo-PTT and real-time MRI monitoring to achieve integration of diagnosis and treatment of TNBC.

Integration of solid-phase microextraction and surface-enhanced Raman spectroscopy for in-vivo screening of polybrominated diphenyl ether.

The monitoring of polybrominated diphenyl ethers (PBDEs) is of great significance owing to their high persistence, bioaccumulation, and toxicity to humans and animals. In this study, a sensitive and reproducible probe that integrates solid-phase microextraction and surface-enhanced Raman spectroscopy (SPME-SERS) was developed for screening PBDEs in multiphase specimens, including live fish, water, and electrical products. A roughed Cu fiber with an Ag layer was fabricated with dual functions. BDE-15 was readily extracted and detected on the SPME-SERS probe consisting of propanethiol-modified Ag nanoplates on a Cu wire. A clear linear relationship (R2 = 0.988) was established between the SERS intensity at 782 cm-1 and the logarithmic concentrations (from 100 ppb to 100 ppm), with a detection limit of 15 ppb. This proposed method enables continuous in vivo monitoring in fish without complicated pretreatments. The results obtained by this SPME-SERS approach were validated by high-performance liquid chromatography and showed good agreement. This "extracting and detecting" SPME-SERS method provides a potential tool to monitor the occurrence, formation, and migration of PBDEs.

Rapid identification and quantification of diquat in biological fluids within 30 s using a portable Raman spectrometer.

Rapid detection of diquat (DQ) is essential in clinical diagnosis and rescue. Here, we developed a fast, simple-yet-practical detection strategy for the reliable identification and quantification of DQ in biological fluids. Based on surface-enhanced Raman spectroscopy (SERS), point-of-care detection was realized under the acidic condition with gold nanoparticles as the substrate. Under optimal experimental conditions, the detection limits of the strategy were 17.5 ppb and 1.99 ppm in human urine and gastric juice, respectively. High specificity and selectivity of the SERS strategy were demonstrated using common pesticides and coexisting biological substances. The method was also used to detect biofluids from 5 patients and urine samples from 10 healthy volunteers. The results were in high agreement with spectrophotometric and clinical liquid chromatography-mass spectrometry methods. The volume of urine samples required for this technique is merely 20 µL, and no preparation of the samples is required. Compared to traditional methods used in clinical settings, SERS-based methods are capable of real-time measurements that accurately provide rapid detection and response in non-laboratory settings, with great potential for on-site and point-of-care testing.

Rapid and robust analysis of aristolochic acid I in Chinese medicinal herbal preparations by surface-enhanced Raman spectroscopy.

The use of Chinese herbs containing aristolochic acid can induce the exchange of adenine and thymine in gene mutations and even cause liver cancer. To eliminate the harm of aristolochic acids (AAs) to humans, a rapid and robust method of AAs screening is a prerequisite. In this work, a facile and robust Surface-enhanced Raman spectroscopy (SERS) method was used for the qualitative and quantitative detection of AAs in Chinese medicinal herbal preparations based on the mandelic acid modified Ag nanoparticles SERS substrate. Qualitative and quantitative SERS detection of Aristolochic acid I (AAI) was achieved with a good linear relationship ranging from 0.2 - 120.0 µM and a limit of detection (LOD) of 0.06 µM. The proposed method demonstrates a refined strategy for sensitivity analysis of AAs with the advantages of easy operation, time-saving, high sensitivity, and molecular specificity, making it a preferred platform for the screening of AAI in regular inspections of herbal products and regulatory supervision of the supply chain.

Synergistic ferroptosis-gemcitabine chemotherapy of the gemcitabine loaded carbonaceous nanozymes to enhance the treatment and magnetic resonance imaging monitoring of pancreatic cancer.

Pancreatic adenocarcinoma (PDAC) is one of the deadliest cancers, and it is resistant to most conventional antineoplastic therapies. To address this challenge, gemcitabine (Gem)-loaded carbonaceous nanoparticles (MFC-Gem) as nanozymes and a theranostic platform were fabricated and used for MR-guided ferroptosis-chemo synergetic therapy of PDAC. As a biocompatible carrier, MFC-Gem nanoparticles are regarded as peroxidase-like and glutathione peroxidase-like nanozymes that promote ferroptosis therapy by effectively generating ROS and consuming GSH. Meanwhile, the combination of MnFe2O4 and Gem can markedly enhance synergetic therapy by both ferroptosis and Gem chemotherapy. MFC-Gem has higher magnetic susceptibility and was used for simultaneous magnetic resonance imaging (MRI) monitoring of the PDAC treatment. In conclusion, these salient features unequivocally indicate that this biocompatible nanotheranostic system has cooperative and enhancing chemotherapy effects for anti-PDAC therapy with simultaneous MRI monitoring. STATEMENT OF SIGNIFICANCE: Pancreatic adenocarcinoma (PDAC) is one of the deadliest cancers, and it is resistant to most conventional antineoplastic therapies. To address this challenge, gemcitabine (Gem)-loaded carbonaceous nanoparticles (MFC-Gem) as nanozymes and a theranostic platform were fabricated and used for MR-guided ferroptosis-chemo synergetic therapy of PDAC. i) MFC nanoparticles are regarded as peroxidase-like and glutathione peroxidase-like nanozymes that enhance ferroptosis therapy by effectively generating ROS and consuming GSH. ii) The combination of MnFe2O4 and Gem can markedly enhance synergetic therapy by both ferroptosis and Gem chemotherapy. iii) MFC-Gem has higher magnetic susceptibility and was used for simultaneous magnetic resonance imaging (MRI) monitoring of the PDAC treatment.

Carbon aerogel from forestry biomass as a peroxymonosulfate activator for organic contaminants degradation.

The carbon catalyst has been widely used as a peroxymonosulfate (PMS) activator to degrade organic contaminants. The biomass carbon aerogel (CA) derived from poplar powder was synthesized in this study. CA with three-dimensional structure exhibited an excellent degradation performance of PMS activation for different types of organic contaminants including bisphenol A (BPA), rhodamine 6 G, phenol, and p-chlorophenol with the removal efficiencies up to 91%, 100%, 100%, and 60% within 60 min, respectively. It was found that singlet oxygen (1O2) dominated the non-radical pathway worked for BPA removal in CA/PMS system. The possible mechanism for PMS activation was discussed. A portion of 1O2 was produced through the transformation of superoxide radical (O2•-) in CA/PMS system. Electronic impedance spectroscopy (EIS) proved that the hierarchical structure of CA contributed to the electron transfer process for PMS activation. The ketonic/carbonyl groups (CË­O) on the surface of CA could serve as a possible active site to facilitate the generation of 1O2. In addition, CA showed superior degradation performance in actual water bodies and reusability with high-temperature regeneration treatment. This study developed an efficient and environmentally benign catalyst for water remediation of organic pollutants.

Carbon-nitrogen conjugate-composited Cu1.8S with enhanced peroxidase-like activity for the colorimetric detection of hydrogen peroxide and glutathione.

In this work, cystine-glucose Maillard conjugates were composited with Cu1.8S microspheres (Cu1.8S-cgmc) to achieve higher sensitivity for the colorimetric analysis. Enhanced peroxidase-like activity was obtained in Cu1.8S-cgmc with a carbon elemental ratio of 1.83% compared to bare Cu1.8S. The catalytic activity of Cu1.8S-cgmc followed Michaelis-Menten kinetic behavior. The Michaelis-Menten constants of Cu1.8S-cgmc on the substrate was over 2-fold lower than that of the bare Cu1.8S, indicating the higher affinity of Cu1.8S-cgmc. The adsorption equilibrium constant of Cu1.8S-cgmc on the substrate was 9.89-fold higher than that of bare Cu1.8S based on thermodynamic investigations. The conjugated structure and carboxyl, hydroxyl and amino groups on Cu1.8S-cgmc improved its hydrophilicity and adsorption on the substrate. The affinity-improved Cu1.8S-cgmc was applied as a peroxidase mimic in colorimetric detection with promoted sensitivity. Compared to bare Cu1.8S, Cu1.8S-cgmc had a 25.5-fold and 19.8-fold lower LOD for H2O2 and glutathione, respectively. The Cu1.8S-cgmc-based colorimetric method showed excellent sensitivity and accuracy in practical colorimetric detection.

Ag@WS2 quantum dots for Surface Enhanced Raman Spectroscopy: Enhanced charge transfer induced highly sensitive detection of thiram from honey and beverages.

Novel SERS substrates is urgently in demand for rapid and sensitive analysis of toxic agrochemicals from food. In this work, a monodispersed tungsten disulfide quantum dots modified silver nanosphere (Ag@WS2QD) was prepared and used as SERS substrate. Ag@WS2QD generated uniform and stable SERS signals within 2 min, displaying great promise in "mixing and reading" detection. Compared to unmodified colloidal silver nanoparticles, 4 times higher analytical enhancement factor was found in Ag@WS2QD. Density functional theory calculation verified the enhanced charge transfer within the coupling systems of molecule-Ag@WS2QD. Besides, the unique surface properties are beneficial for the enrichment of specific molecule. Both the chemical extraction and enhanced charge transfer contributes to rapid and sensitive SERS detection of Ag@WS2QD. A "mixing and reading" SERS method for thiram from honey and four kinds of juice was developed from Ag@WS2QD, showing great promise for rapid and direct SERS detection for toxic agrochemicals and further applications.

Caramelized carbonaceous shell-coated γ-Fe2O3 as a magnetic solid-phase extraction sorbent for LC-MS/MS analysis of triphenylmethane dyes.

Carbonaceous shell-coated γ-Fe2O3 nanoparticles (γ-Fe2O3@CNM) were synthesized from glucose caramelization and used as a novel magnetic solid-phase extraction medium for malachite green and crystal violet in environmental water. Malachite green and crystal violet were absorbed on to γ-Fe2O3@CNM by electrostatic and π-interactions. The morphologies, pore structures, surface functional groups, and magnetic properties of γ-Fe2O3@CNM were characterized by TEM, FTIR, hysteresis regression, Brunauer-Emmet-Teller analysis, zeta potential, XPS, and XRD. The magnetic solid-phase extraction procedure was optimized by extraction pH, absorption time, desorption solvent, and desorption time. The absorption capacities (qmax values) for malachite green and crystal violet were 34.2 and 27.9 mg g-1, respectively. After magnetic solid-phase extraction, malachite green and crystal violet were determined by LC-MS/MS. The analytical method was validated with a linear range of 0.02-20 ng mL-1, enrichment factor of 25.8 and 25.4, method detection limit of 0.004 ng mL-1, and intra-day precisions of 2.1% and 2.6% for malachite green and crystal violet, respectively. The relative recovery was found to be 73.4-101.5% for malachite green and 83.1-102.7% for crystal violet upon the application of the magnetic solid-phase extraction method to real water samples from lake, spring, sea, fishpond, and industrial waste. Graphical abstract Caramelized-carbon-coated magnetic nanoparticles are used as novel extraction medium based on electrostatic and π-interactions. It is porous, amphiphilic, electronegative, magnetically strong, and features abundant absorption site. These characteristics stimulate mass transfer and result in a useful MSPE method in environmental analysis.

Magnetic multiwalled carbon nanotubes with controlled release of epirubicin: an intravesical instillation system for bladder cancer.

BACKGROUND: Traditional intravesical instillation treatment in bladder cancer has limited efficacy, which results in a high frequency of recurrence. PURPOSE: The aim of this study was to report on an epirubicin (EPI)-loaded magnetic multi-walled carbon nanotube (mMWCNTs-EPI) system for intravesical instillation in place of the current formulation. METHODS: The mMWCNTs-EPI system was formulated with carboxylated MWCNTs, Fe3O4 magnetic nanoparticles, and EPI. Features and antitumor activity of the system were investigated. RESULTS: Under the effect of external magnets, the mMWCNTs-EPI system showed sustained release and prolonged retention behavior and better antitumor activity than free EPI. The mMWCNTs-EPI system had higher efficiency in enhancing cytotoxicity and inhibiting proliferation in vitro and in vivo than free EPI. Our studies also revealed the atoxic nature of mMWCNTs. CONCLUSION: These findings suggested that mMWCNTs are effective intravesical instillation agents with great potential for clinical application.

A novel sandwiched electrochemiluminescence immunosensor for the detection of carcinoembryonic antigen based on carbon quantum dots and signal amplification.

In this study, a novel sandwiched electrochemiluminescence (ECL) immunosensor for the detection of carcinoembryonic antigen (CEA) was developed. The nanocomposite of polydopamine and Ag nanoparticles (PDA-AgNPs) was prepared by the redox reaction between Ag+ and dopamine. This nanocomposite not only provided an effective matrix for the immobilization of primary antibody (Ab1) but also enhanced the conductivity of the electrode. Carbon quantum dots (CQDs) were immobilized on the poly(ethylenimine) functionalized graphene oxide (PEI-GO) through amido-bond. Then Au nanoparticles were decorated on the CQDs modified PEI-GO matrix, and the resulted complex AuNPs/CQDs-PEI-GO was introduced to link secondary antibody (Ab2). The CQDs can be connected to the electrode surface through the combination of CEA with Ab1 and Ab2, and then the amplified electrochemiluminescence signal of CQDs was obtained with the synergistic effect of AgNPs, polydopamine, AuNPs and PEI-GO. Under the optimal conditions, the ECL intensity was proportional to the logarithm value of CEA concentration in the linear range from 5pgmL-1 to 500ngmL-1 with a detection limit of 1.67pgmL-1 for CEA detection. The immunosensor was applied for the CEA detection in real samples with satisfactory results. The proposed ECL immunosensor showed good performance with high sensitivity, specificity, reproducibility, stability and will be potential in clinical detection.