Construction of an exosome-functionalized graphene oxide based composite bionic smart drug delivery system and its anticancer activity

Graphene oxide has covalently modified by chito oligosaccharides and γ-polyglutamic acid to form GO-CO-γ-PGA, which exhibits excellent performance as a drug delivery carrier, but this carrier did not have the ability to actively target. In this study, the targeting property of breast cancer tumor cell exosomes was exploited to give GO-CO-γ-PGA the ability to target breast tumor cells (MDA-MB-231), and the drug mitoxantrone (MIT) was loaded to finally form EXO-GO-CO-γ-PGA-MIT with a loading capacity of 1.39 mg/mg. The pH response of EXO-GO-CO-γ-PGA showed a maximum cumulative release rate of 56.59% (pH 5.0) and 6.73% (pH 7.4) for MIT at different pH conditions. pH 7.4). In vitro cellular assays showed that EXO-GO-CO-γ-PGA-MIT was more potent in killing MDA-MB-231 cells due to its targeting ability and had a significantly higher pro-apoptotic capacity compared to GO-CO-γ-PGA-MIT. The results showed that this bionic nano-intelligent drug delivery system has good drug slow release function, can increase the local drug concentration of tumor and enhance the pro-apoptotic ability of MIT, so this newly synthesized bionic drug delivery carriers (EXO-GO-CO-γ-PGA-MIT) has potential application in breast cancer treatment.

PyCO2SYS v1.8: marine carbonate system calculations in Python

Oceanic dissolved inorganic carbon (TC) is the largest pool of carbon that substantially interacts with the atmosphere on human timescales. Oceanic TC is increasing through uptake of anthropogenic carbon dioxide (CO2), and seawater pH is decreasing as a consequence. Both the exchange of CO2 between the ocean and atmosphere and the pH response are governed by a set of parameters that interact through chemical equilibria, collectively known as the marine carbonate system. To investigate these processes, at least two of the marine carbonate system's parameters are typically measured – most commonly, two from TC, total alkalinity (AT), pH, and seawater CO2 fugacity (fCO2; or its partial pressure, pCO2, or its dry-air mole fraction, xCO2) – from which the remaining parameters can be calculated and the equilibrium state of seawater solved. Several software tools exist to carry out these calculations, but no fully functional and rigorously validated tool written in Python, a popular scientific programming language, was previously available. Here, we present PyCO2SYS, a Python package intended to fill this capability gap. We describe the elements of PyCO2SYS that have been inherited from the existing CO2SYS family of software and explain subsequent adjustments and improvements. For example, PyCO2SYS uses automatic differentiation to solve the marine carbonate system and calculate chemical buffer factors, ensuring that the effect of every modelled solute and reaction is accurately included in all its results. We validate PyCO2SYS with internal consistency tests and comparisons against other software, showing that PyCO2SYS produces results that are either virtually identical or different for known reasons, with the differences negligible for all practical purposes. We discuss insights that guided the development of PyCO2SYS: for example, the fact that the marine carbonate system cannot be unambiguously solved from certain pairs of parameters. Finally, we consider potential future developments to PyCO2SYS and discuss the outlook for this and other software for solving the marine carbonate system. The code for PyCO2SYS is distributed via GitHub (https://github.com/mvdh7/PyCO2SYS, last access: 23 December 2021) under the GNU General Public License v3, archived on Zenodo (Humphreys et al., 2021), and documented online (https://pyco2sys.readthedocs.io/en/latest/, last access: 23 December 2021).

Comparative proteomic analysis of Fusarium oxysporum f. sp. cubense strains (Foc R1 and Foc TR4) provides better insights into mechanisms of their virulence, habitat adaptation and pathogenesis

Fusarium oxysporum f. sp. cubense (Foc), a devastative soil-borne fungal pathogen causing vascular wilt (i.e. Panama disease) which leads to severe crop losses in most of the banana-growing regions of the world. As there is no single source of effective management practices available so far, understand the pathogenicity of the organism may help in designing effective control measures through molecular approaches. The study aims to compare the proteome of the two pathogenic Foc virulent strains, Race 1 (Foc R1) and tropical race 4 (Foc TR4) that are capable of infecting the Cavendish group of bananas using 2-dimensional (2-D) gel electrophoresis, MALDI-TOF/MS and MS/MS analysis. The results of the study revealed that the proteins, peroxiredoxins, NAD-aldehyde dehydrogenase (NAD-ALDH), MAPK protein, pH-response regulator protein palA/rim-20 and isotrichodermin C15 hydroxylase have shared homology with the fungal proteins, which regulate the osmotic stress response, signal transduction, root colonization and toxin biosynthesis. These are the important functions for the pathogen survival in an unfavourable environment, and successful establishment and infection of the banana host. The present study also identified several putative pathogenicity related proteins in both Foc R1 and Foc TR4. Specifically, certain Foc TR4 specific putative pathogenicity related proteins, phytotoxins biosynthesis gene, fructose 1,6-bisphosphate aldolase class II, Synembryn-like proteins found to contribute strong virulence. Overexpression or knockout of the elective genes could help in devising better control measures for the devastative pathogens in the future. To the best of our knowledge, this is the first report on the proteomics of Foc R1 and Foc TR4 strains of Indian origin that infect Cavendish bananas.

The Layered Encapsulation of Vitamin B2 and β-Carotene in Multilayer Alginate/Chitosan Gel Microspheres: Improving the Bioaccessibility of Vitamin B2 and β-Carotene

This research underlines the potential of alginate multilayered gel microspheres for the layered encapsulation and the simultaneous delivery of vitamin B2 (VB) and β-carotene (BC). Chitosan was used to improve the stability and controlled release ability of alginate-based gel microspheres. It was shown that a clear multilayered structure possessed the characteristics of pH response, and excellent thermal stability. The sodium alginate concentration and the number of layers had notable effects on mechanical properties and particle size of gel microspheres. Fourier-transform infrared spectroscopy and X-ray diffraction analyses further proved that VB and BC were encapsulated within the gel microspheres. Compared with the three-layer VB-loaded gel microspheres, the total release of VB from the three-layer VB and BC-loaded gel decreased from 93.23 to 85.58%. The total release of BC from the three-layer VB and BC-loaded gel increased from 66.11 to 69.24% compared with three-layer BC-loaded gel. The simultaneous encapsulation of VB and BC in multilayered gel microspheres can markedly improve their bioaccessibility and bioavailability. These results showed the multilayer gel microspheres synthesized herein have potential for applications in the layered encapsulation and simultaneous delivery of various bioactive substances to the intestinal tract.

Fabrication of an All-Solid-State Ammonium Paper Electrode Using a Graphite-Polyvinyl Butyral Transducer Layer

A planar solid-state ammonium-selective electrode, employing a composite mediator layer of graphite particles embedded in a polyvinyl butyral matrix on top of an inkjet-printed silver electrode, is presented in this paper. The effect of graphite powder mass fraction on the magnitude of the potentiometric response of the sensor was systematically verified using a batch-mode and a flow injection measurement setup. Under steady-state conditions, the paper electrode provided a Nernstian response of 57.30 mV/pNH4 over the concentration range of 10−5 M to 10−1 M with a detection limit of 4.8 × 10−6 M, while the analytical performance of the array in flow mode showed a narrower linear range (10−4 M to 10−1 M; 60.91 mV/pNH4 slope) with a LOD value of 5.6 × 10−5 M. The experimental results indicate that the prepared electrode exhibited high stability and fast response to different molar concentrations of ammonium chloride solutions. The pH-response of the paper NH4-ISE was also investigated, and the sensor remained stable in the pH range of 2.5–8.5. The potentiometric sensor presented here is simple, lightweight and inexpensive, with a potential application for in-situ analysis of environmental water samples.

A polydopamine nanomedicine used in photothermal therapy for liver cancer knocks down the anti-cancer target NEDD8-E3 ligase ROC1 (RBX1)

Knocking down the oncogene ROC1 with siRNA inhibits the proliferation of cancer cells by suppressing the Neddylation pathway. However, methods for delivering siRNA in vivo to induce this high anticancer activity with low potential side effects are urgently needed. Herein, a folic acid (FA)-modified polydopamine (PDA) nanomedicine used in photothermal therapy was designed for siRNA delivery. The designed nanovector can undergo photothermal conversion with good biocompatibility. Importantly, this genetic nanomedicine was selectively delivered to liver cancer cells by FA through receptor-mediated endocytosis. Subsequently, the siRNA cargo was released from the PDA nanomedicine into the tumor microenvironment by controlled release triggered by pH. More importantly, the genetic nanomedicine not only inhibited liver cancer cell proliferation but also promoted liver cell apoptosis by slowing ROC1 activity, suppressing the Neddylation pathway, enabling the accumulation of apototic factor ATF4 and DNA damage factor P-H2AX. Combined with photothermal therapy, this genetic nanomedicine showed superior inhibition of the growth of liver cancer in vitro and in vivo. Taken together, the results indicate that this biodegradable nanomedicine exhibits good target recognition, an effective pH response, application potential for genetic therapy, photothermal imaging and treatment of liver cancer. Therefore, this work contributes to the design of a multifunctional nanoplatform that combines genetic therapy and photothermal therapy for the treatment of liver cancer.

Multicolor PEGDA/LCNF Hydrogel in the Presence of Red Cabbage Anthocyanin Extract

Colorimetric indicator gels were developed by incorporating anthocyanin (AC) obtained from red cabbage into poly (ethylene glycol) diacrylate (PEGDA)-based hydrogel containing lignocellulose nanofiber (LCNF). The PEGDA-based hydrogel was prepared by mixing all of the mentioned components at the specific composition, and the hydrogels were cured under UV light (245 nm) for 1 min. The pH-response, UV absorption, swelling ratio, and mechanical properties of PEGDA/LCNF were determined. It was further found that PEGDA and LCNF mount play an important role in adjusting the mechanical properties of PEGDA/LCNF. In general, the presence of LCNF improved the mechanical properties and swelling ratio of PEGDA. The incorporation of red cabbage anthocyanin into the PEGDA/LCNF film showed multicolor response when specific pH buffers were introduced. Based on the multicolor response of PEGDA/LCNF/CA, this gel film indicator can be developed as a food freshness indicator that focuses on the detection of ammonia and amine compound.

Mesoporous Silica Encapsulated Iron Oxide-Silver Heterodimeric Nanoparticles and Their Applications in Multi-Responsive Drug Release

Background Metal based nanomaterials play essential roles in the fields of cancer diagnosis and therapy, drug delivery and exploration. As a novel kind of metal nanocomposites, magnetic-plasmonic nanohybrids are promising candidates in combined therapy. However, few studies have demonstrated the multi-responsive drug delivery properties of the nanohybrids. In this work, novel Fe3O4-Ag heterodimer nanoparticles coated with mesoporous SiO2 were prepared for multi-responsive drug release applications. Results Seed growth method was employed to form the heterodimer particles, and a layer of mesoporous silica was coated on the particle to improve the biocompatibility of metal nanoparticles, which also acted as drug loading and release component. Characterized via infrared spectroscopy, X-Ray diffraction and transmission electron microscopy, the particles were confirmed to appear a Janus like structure with Fe3O4 and Ag hemispheres encapsulating in silica. Doxorubicin hydrochloride (DOX) was loaded on the surface of the particles for drug delivery. The drug loading efficiency, release performance and the apoptosis action of the particles on MCF-7 cells were investigated in vitro. The results showed that DOX was successfully loaded on the particles with encapsulation efficiency of 88.3% and drug loading of 30.6%. And the release amount after 48 h increased from 10.05 ± 0.19% to 68.53 ± 8.20% as the environment was tuned to acidic, indicating an obvious pH response of the particles. Simultaneously, due to the photothermal effect of Ag hemispheres, the particles had exhibited an enhanced drug release stimulated by 808 nm near infrared (NIR) irradiation. And the results of apoptosis assay were in accord with the drug release profiles. Besides, the particles could well respond to an external magnetic field, which is beneficial to particle location or recovery. Conclusion The as-prepared particles exhibit good magnetic and photothermal properties originating from Fe3O4 and Ag hemispheres respectively, which are desired features in magnetic hyperthermia and photothermal therapy. The particles also possess pH and NIR light responsive drug release properties, enabling triggered and targeted drug delivery.

Acid-base transport model of interfacial reactions for dynamic pH response quantification and regulation

The dynamic pH response resulting from acid-base transport of interfacial reactions greatly influences the kinetic performance and process mechanism, but its theoretical foundation is lacked. Herein, a generalized acid-base transport model is established owing to the success in deriving buffer transport equations and is experimentally through the relationships of buffer transport limiting current versus solution pH and buffer concentration (CB). The relationships bring forth the parameter determination methods of buffers with the superiority of facile survey of practical parameter values. Based on model calculations, the dynamic pH response is drawn as a j‒pH diagram to show the buffer transport law in the full pH range, highlighting the rate-limiting effect. The buffer operation principles are graphically presented as CB‒ΔpH diagrams to aid economic buffer applications. This study has laid the foundation for quantification and regulation of dynamic pH response and is of wide interest to the chemistry encompassing interfacial processes.