Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

ELSSI: parallel SNP-SNP interactions detection by ensemble multi-type detectors.

With the development of high-throughput genotyping technology, single nucleotide polymorphism (SNP)-SNP interactions (SSIs) detection has become an essential way for understanding disease susceptibility. Various methods have been proposed to detect SSIs. However, given the disease complexity and bias of individual SSI detectors, these single-detector-based methods are generally unscalable for real genome-wide data and with unfavorable results. We propose a novel ensemble learning-based approach (ELSSI) that can significantly reduce the bias of individual detectors and their computational load. ELSSI randomly divides SNPs into different subsets and evaluates them by multi-type detectors in parallel. Particularly, ELSSI introduces a four-stage pipeline (generate, score, switch and filter) to iteratively generate new SNP combination subsets from SNP subsets, score the combination subset by individual detectors, switch high-score combinations to other detectors for re-scoring, then filter out combinations with low scores. This pipeline makes ELSSI able to detect high-order SSIs from large genome-wide datasets. Experimental results on various simulated and real genome-wide datasets show the superior efficacy of ELSSI to state-of-the-art methods in detecting SSIs, especially for high-order ones. ELSSI is applicable with moderate PCs on the Internet and flexible to assemble new detectors. The code of ELSSI is available at https://www.sdu-idea.cn/codes.php?name=ELSSI.

Localized high-concentration electrolytes get more localized through micelle-like structures.

Liquid electrolytes in batteries are typically treated as macroscopically homogeneous ionic transport media despite having a complex chemical composition and atomistic solvation structures, leaving a knowledge gap of the microstructural characteristics. Here, we reveal a unique micelle-like structure in a localized high-concentration electrolyte, in which the solvent acts as a surfactant between an insoluble salt in a diluent. The miscibility of the solvent with the diluent and simultaneous solubility of the salt results in a micelle-like structure with a smeared interface and an increased salt concentration at the centre of the salt-solvent clusters that extends the salt solubility. These intermingling miscibility effects have temperature dependencies, wherein a typical localized high-concentration electrolyte peaks in localized cluster salt concentration near room temperature and is used to form a stable solid-electrolyte interphase on a Li metal anode. These findings serve as a guide to predicting a stable ternary phase diagram and connecting the electrolyte microstructure with electrolyte formulation and formation protocols of solid-electrolyte interphases for enhanced battery cyclability.

Pharmacokinetic/Pharmacodynamic Assessment of the Structural Refinement of Clopidogrel Focusing on the Balance between Bioactivation and Deactivation.

The delicate balance between ischemic and bleeding risks is a critical factor in antiplatelet therapy administration. Clopidogrel and prasugrel, belonging to the thienopyridine class of antiplatelet drugs, are known for their variability in individual responsiveness and high incidence of bleeding events, respectively. The present study is centered on the development and assessment of a range of deuterated thienopyridine derivatives, leveraging insights from structure-pharmacokinetic relationships of clopidogrel and prasugrel. Our approaches were grounded in the molecular framework of clopidogrel and incorporated the C2-pharmacophore design from prasugrel. The selection of ester or carbamate substituents at the C2-position facilitated the generation of the 2-oxointermediate through hydrolysis, akin to prasugrel, thereby bypassing the issue of CYP2C19 dependency. The bulky C2-pharmacophore in our approach distinguishes itself from prasugrel's acetyloxy substituent by exhibiting a moderated hydrolysis rate, resulting in a more gradual formation of the active metabolite. Excessive and rapid release of the active metabolite, believed to be linked with an elevated risk of bleeding, is thus mitigated. Our proposed structural modification retains the hydrolysis-sensitive methyl ester of clopidogrel but substitutes it with a deuterated methyl group, shown to effectively reduce metabolic deactivation. Three promising compounds demonstrated a pharmacokinetic profile similar to that of clopidogrel at four times the dose, while also augmenting its antiplatelet activity. SIGNIFICANCE STATEMENT: Inspired by the structure-pharmacokinetic relationship of clopidogrel and prasugrel, a range of clopidogrel derivatives were designed, synthesized, and assessed. Among them, three promising compounds have been identified, striking a delicate balance between efficacy and safety for antiplatelet therapy. Additionally, the ozagrel prodrug conjugate was discovered to exert a synergistic therapeutic effect alongside clopidogrel.

Assessment of sedation by automated pupillometry in critically ill patients: a prospective observational study.

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.

Effects of fluorinated solvents on electrolyte solvation structures and electrode/electrolyte interphases for lithium metal batteries.

Electrolyte is very critical to the performance of the high-voltage lithium (Li) metal battery (LMB), which is one of the most attractive candidates for the next-generation high-density energy-storage systems. Electrolyte formulation and structure determine the physical properties of the electrolytes and their interfacial chemistries on the electrode surfaces. Localized high-concentration electrolytes (LHCEs) outperform state-of-the-art carbonate electrolytes in many aspects in LMBs due to their unique solvation structures. Types of fluorinated cosolvents used in LHCEs are investigated here in searching for the most suitable diluent for high-concentration electrolytes (HCEs). Nonsolvating solvents (including fluorinated ethers, fluorinated borate, and fluorinated orthoformate) added in HCEs enable the formation of LHCEs with high-concentration solvation structures. However, low-solvating fluorinated carbonate will coordinate with Li+ ions and form a second solvation shell or a pseudo-LHCE which diminishes the benefits of LHCE. In addition, it is evident that the diluent has significant influence on the electrode/electrolyte interphases (EEIs) beyond retaining the high-concentration solvation structures. Diluent molecules surrounding the high-concentration clusters could accelerate or decelerate the anion decomposition through coparticipation of diluent decomposition in the EEI formation. The varied interphase features lead to significantly different battery performance. This study points out the importance of diluents and their synergetic effects with the conductive salt and the solvating solvent in designing LHCEs. These systematic comparisons and fundamental insights into LHCEs using different types of fluorinated solvents can guide further development of advanced electrolytes for high-voltage LMBs.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

From Body Monitoring to Biomolecular Sensing: Current Progress and Future Perspectives of Triboelectric Nanogenerators in Point-of-Care Diagnostics.

In the constantly evolving field of medical diagnostics, triboelectric nanogenerators (TENGs) stand out as a groundbreaking innovation for simultaneously harnessing mechanical energy from micromovements and sensing stimuli from both the human body and the ambient environment. This advancement diminishes the dependence of biosensors on external power sources and paves the way for the application of TENGs in self-powered medical devices, especially in the realm of point-of-care diagnostics. In this review, we delve into the functionality of TENGs in point-of-care diagnostics. First, from the basic principle of how TENGs effectively transform subtle physical movements into electrical energy, thereby promoting the development of self-powered biosensors and medical devices that are particularly advantageous for real-time biological monitoring. Then, the adaptable design of TENGs that facilitate customization to meet individual patient needs is introduced, with a focus on their biocompatibility and safety in medical applications. Our in-depth analysis also covers TENG-based biosensor designs moving toward exceptional sensitivity and specificity in biomarker detection, for accurate and efficient diagnoses. Challenges and future prospects such as the integration of TENGs into wearable and implantable devices are also discussed. We aim for this review to illuminate the burgeoning field of TENG-based intelligent devices for continuous, real-time health monitoring; and to inspire further innovation in this captivating area of research that is in line with patient-centered healthcare.

Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.

AIMS: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity. METHODS: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated. RESULTS: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 µg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group. CONCLUSION: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

Screening Antioxidant Components in Different Parts of Dandelion Using Online Gradient Pressure Liquid Extraction Coupled with High-Performance Liquid Chromatography Antioxidant Analysis System and Molecular Simulations.

Utilizing online gradient pressure liquid extraction (OGPLE) coupled with a high-performance liquid chromatography antioxidant analysis system, we examined the antioxidative active components present in both the aerial parts and roots of dandelion. By optimizing the chromatographic conditions, we identified the ferric reducing-antioxidant power system as the most suitable for online antioxidant reactions in dandelion. Compared to offline ultrasonic extraction, the OGPLE method demonstrated superior efficiency in extracting chemical components with varying polarities from the samples. Liquid chromatography-mass spectrometry revealed twelve compounds within the dandelion samples, with nine demonstrating considerable antioxidant efficacy. Of these, the aerial parts and roots of dandelion contained nine and four antioxidant constituents, respectively. Additionally, molecular docking studies were carried out to investigate the interaction between these nine antioxidants and four proteins associated with oxidative stress (glutathione peroxidase, inducible nitric oxide synthase, superoxide dismutase, and xanthine oxidase). The nine antioxidant compounds displayed notable binding affinities below -5.0 kcal/mol with the selected proteins, suggesting potential receptor-ligand interactions. These findings contribute to enhancing our understanding of dandelion and provide a comprehensive methodology for screening the natural antioxidant components from herbs.

Effect of ph on migration patterns and degradation pathways of sulfamethazine in soil systems.

Sulfonamide antibiotics (SAs) are widely used antimicrobial agents in livestock and aquaculture, and most of them entering the animal's body will be released into the environment as prodrugs or metabolites, which ultimately affect human health through the food chain. Both acid deposition and salinization of soil may have an impact on the migration and degradation of antibiotics. Sulfamethazine (SM2), a frequently detected compound in agricultural soils, has a migration and transformation process in the environment that is closely dependent on environmental pH. Nevertheless, scarcely any studies have been conducted on the effect of soil pH changes on the environmental behavior of sulfamethazine. We analyzed the migration and degradation mechanisms of SM2 using simulation experiments and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) techniques. The results showed that acidic conditions limited the vertical migration of sulfadimidine, and SM2 underwent different reaction processes under different pH conditions, including S-C bond breaking, S-N bond hydrolysis, demethylation, six-membered heterocyclic addition, methyl hydroxylation and ring opening. The study of the migration pattern and degradation mechanism of SM2 under different pH conditions can provide a solid theoretical basis for assessing the pollution risk of sulfamethazine degradation products under acid rain and saline conditions, and provide a guideline for remediation of antibiotic contamination, so as to better prevent, control and protect groundwater resources.

Iron-inhibited autophagy via transcription factor ZFP27 in Parkinson's disease.

Parkinson's disease (PD) is a challenge because of the ageing of the population and the disease's complicated pathogenesis. Accumulating evidence showed that iron and autophagy were involved in PD. Nevertheless, the molecular mechanism and role of iron and autophagy in PD are not yet elucidated. In the present study, it was shown that PD mice had significant motor dysfunction, increased iron content, less dopamine neurons and more α-synuclein accumulation in the substantia nigra. Meanwhile, PD mice treated with deferoxamine exhibited less iron content, relieved the dyskinesia and had a significant increase in dopamine neurons and a significant decrease in α-synuclein. Autophagy induced by LC3 was inhibited in PD models with iron treatment. Following verification showed that iron aggregation restrained insulin-like growth factor 2 (IGF2) and transcription factor zinc finger protein 27 (ZFP27) in PD models. In addition, LC3-induced autophagy flux was reduced with ZFP27 knockdown. Furthermore, ZFP27 affected autophagy by regulating LC3 promoter activity. These data suggest that iron deposition inhibits IGF2 and ZFP27 to reduce LC3-induced autophagy, and ultimately decrease dopamine neurons, accelerating PD progression. Our findings provide a novel insight that ZFP27-mediated iron-related autophagy and IGF2 may activate the downstream kinase gene to trigger autophagy in the PD model.

Thermal-Driven Soft-Contact Triboelectric Nanogenerator for Energy Harvesting and Industrial Cooling Water Monitoring.

In this paper, a quaternary dielectric soft-contact rotary triboelectric nanogenerator (QDSR-TENG) of low frictional resistance is fabricated for combining TENG with a shape memory alloy (SMA) engine. The introduction of rabbit fur brush and FEP brush results in charge pumps with a partially soft contact structure. Benefiting from the low friction loss of the structure, the QDSR-TENG can operate stably and continually for 100k cycles without significant output degradation. The SMA engine exhibits thermally induced phase transformation and super-elasticity and can be utilized for harnessing waste heat energy. The thermal-driven QDSR-TENG can operate with a water source of 43 °C with a distinguishable response to the variation of temperatures. Such a low starting temperature not only promotes the harvesting of low-grade thermal energy, but also results in a self-monitoring industrial cooling water system. The coupled elastocaloric power and cooling cycle proposed in the thermal-driven QDSR-TENG opens a new paradigm for the application in energy harvesting and smart sensing.

riboCleaner: a pipeline to identify and quantify rRNA read contamination from RNA-seq data in plants.

MOTIVATION: Analysis of gene expression data can be crucial for elucidating biological relationships within living organisms. However, accurate quantification of gene expression relies directly upon the accuracy of the reference genome or transcriptome to which the expression data are mapped. Errors in gene annotation can lead to errors in the quantification of gene expression. One source of gene annotation error in eukaryotes arises from incorrect predictions of messenger RNA gene models within ribosomal DNA (rDNA) regions. RESULTS: Here, we provide examples of how the presence of false gene models in rDNA regions can result in a handful of genes appearing to contribute to >50% of the total transcripts per million values of entire RNA-seq datasets. To this end, we have created riboCleaner, a bioinformatics pipeline designed to identify misannotated gene models in rDNA regions and quantify rRNA-derived reads in RNA-seq data. We also show the applicability of riboCleaner in several plant genome assemblies. AVAILABILITY AND IMPLEMENTATION: We have implemented riboCleaner as a containerized Snakemake workflow. The workflow, instructions for building the container and other documentation are available at https://github.com/basf. The data underlying this article are available in GitHub at https://github.com/basf/riboCleaner. For convenience, a prebuilt Docker image containing riboCleaner is available at https://hub.docker.com/u/basfcontainers. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Function and Regulation of Platelet P2Y12 Receptor.

In addition to the key role in hemostasis and thrombosis, platelets have also been wildly acknowledged as immune regulatory cells and involving in the pathogenesis of inflammation-related diseases. Since purine receptor P2Y12 plays a crucial role in platelet activation, P2Y12 antagonists such as clopidogrel, prasugrel, and ticagrelor have been widely used in cardiovascular diseases worldwide in recent decades due to their potent antiplatelet and antithrombotic effects. Meanwhile, the role of P2Y12 in inflammatory diseases has also been extensively studied. Relatively, there are few studies on the regulation of P2Y12. This review first summarizes the various roles of P2Y12 in the process of platelet activation, as well as downstream effects and signaling pathways; then introduces the effects of P2Y12 in inflammatory diseases such as sepsis, atherosclerosis, cancer, autoimmune diseases, and asthma; and finally reviews the current researches on P2Y12 regulation.

Role of inner solvation sheath within salt-solvent complexes in tailoring electrode/electrolyte interphases for lithium metal batteries.

Functional electrolyte is the key to stabilize the highly reductive lithium (Li) metal anode and the high-voltage cathode for long-life, high-energy-density rechargeable Li metal batteries (LMBs). However, fundamental mechanisms on the interactions between reactive electrodes and electrolytes are still not well understood. Recently localized high-concentration electrolytes (LHCEs) are emerging as a promising electrolyte design strategy for LMBs. Here, we use LHCEs as an ideal platform to investigate the fundamental correlation between the reactive characteristics of the inner solvation sheath on electrode surfaces due to their unique solvation structures. The effects of a series of LHCEs with model electrolyte solvents (carbonate, sulfone, phosphate, and ether) on the stability of high-voltage LMBs are systematically studied. The stabilities of electrodes in different LHCEs indicate the intrinsic synergistic effects between the salt and the solvent when they coexist on electrode surfaces. Experimental and theoretical analyses reveal an intriguing general rule that the strong interactions between the salt and the solvent in the inner solvation sheath promote their intermolecular proton/charge transfer reactions, which dictates the properties of the electrode/electrolyte interphases and thus the battery performances.

Modular Design in Triboelectric Sensors: A Review on the Clinical Applications for Real-Time Diagnosis.

Triboelectric nanogenerators (TENGs) have garnered considerable interest as a promising technology for energy harvesting and stimulus sensing. While TENGs facilitate the generation of electricity from micro-motions, the modular design of TENG-based modular sensing systems (TMSs) also offers significant potential for powering biosensors and other medical devices, thus reducing dependence on external power sources and enabling biological processes to be monitored in real time. Moreover, TENGs can be customised and personalized to address individual patient needs while ensuring biocompatibility and safety, ultimately enhancing the efficiency and security of diagnosis and treatment. In this review, we concentrate on recent advancements in the modular design of TMSs for clinical applications with an emphasis on their potential for personalised real-time diagnosis. We also examine the design and fabrication of TMSs, their sensitivity and specificity, and their capabilities of detecting biomarkers for disease diagnosis and monitoring. Furthermore, we investigate the application of TENGs to energy harvesting and real-time monitoring in wearable and implantable medical devices, underscore the promising prospects of personalised and modular TMSs in advancing real-time diagnosis for clinical applications, and offer insights into the future direction of this burgeoning field.

In-vitro and in-vivo evaluation and anti-colitis activity of esculetin-loaded nanostructured lipid carrier decorated with DSPE-MPEG2000.

OBJECTIVE: Encapsulation of esculetin into DSPE-MPEG2000 carrier was performed to improve its water solubility and oral bioavailability, as well as enhance its anti-inflammatory effect on a mouse model of ulcerative colitis that was induced with dextran sulphate sodium (DSS). METHODS: We determined the in-vitro and in-vivo high-performance liquid chromatographic (HPLC) analysis method of esculetin; Esculetin-loaded nanostructure lipid carrier (Esc-NLC) was prepared using a thin-film dispersion method, wherein a particle size analyser was used to measure the particle size (PS) and zeta potential (ZP) of the Esc-NLC, while a transmission electron microscope (TEM) was employed to observe its morphology. Also, HPLC was used to measure its drug loading (DL), encapsulation efficiency (EE) and the in-vitro release of the preparation, as well as investigate the pharmacokinetic parameters. In addition, its anti-colitis effect was evaluated via histopathological examination of HE-stained sections and detection of the concentrations of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (ß), and IL-6 in serum with ELISA kits. RESULTS: The PS of Esc-NLC was 102.29 ± 0.63 nm with relative standard deviation (RSD) of 1.08% (with poly-dispersity index-PDI of 0.197 ± 0.023), while the ZP was -15.67 ± 1.39 mV with RSD of 1.24%. Solubility of esculetin was improved coupled with prolonged release time. Its pharmacokinetic parameters were compared with that of free esculetin, wherein the maximum concentration of the drug in plasma was increased by 5.5 times. Of note, bioavailability of the drug was increased by 1.7 times, while the half-life was prolonged by 2.4 times. In the anti-colitis efficacy experiment, the mice in Esc and Esc-NLC groups exhibited significantly reduced levels of TNF-α, IL-1ß, and IL-6 in their sera comparable to the DSS group. Colon histopathological examination revealed that mice with ulcerative colitis in both Esc and Esc-NLC groups displayed improved inflammation, amid the Esc-NLC groups having the best prophylactic treatment effect. CONCLUSION: Esc-NLC could ameliorate DSS-induced ulcerative colitis by improving bioavailability, prolonging drug release time and regulating cytokine release. This observation confirmed the potential of Esc-NLC to reduce inflammation in ulcerative colitis, albeit the need for follow-up research to verify the application of this strategy to clinical treatment of ulcerative colitis.

Photothermal Therapy Mediated Hybrid Membrane Derived Nano-formulation for Enhanced Cancer Therapy.

Emodin is applied as an antitumor drug in many tumor therapies. However, its pharmacology performances are limited due to its low solubility. Herein, we fused erythrocyte and macrophage to form a hybrid membrane (EMHM) and encapsulated emodin to form hybrid membrane-coated nanoparticles. We employed glycyrrhizin to increase the solubility of emodin first and prepared the hybrid membrane nanoparticle-coated emodin and glycyrrhizin (EG@EMHM NPs) which exhibited an average particle size of 170 ± 20 nm and encapsulation efficiency of 98.13 ± 0.67%. The half-inhibitory concentrations (IC50) of EG@EMHM NPs were 1.166 µg/mL, which is half of the free emodin. Based on the photosensitivity of emodin, the reactive oxygen species (ROS) results disclosed that ROS levels of the photodynamic therapy (PDT) section were higher than the normal section (P < 0.05). Compared to the normal section, PDT-mediated EG@EMHM NPs could induce an early stage of apoptosis of B16. The western blot and flow cytometry results verified that PDT-mediated EG@EMHM NPs can significantly improve the solubility of emodin and perform a remarkably antitumor effect on melanoma via BAX and BCL-2 pathway. The application of the combined chemical and PDT therapy could provide an improving target therapy for cutaneous melanoma and also may offer an idea for other insoluble components sources of traditional Chinese medicine. Schematic of EG@EMHM NPs formulation.

Microfluidic Generation of Near-Infrared Photothermal Vitexin/ICG Liposome with Amplified Photodynamic Therapy.

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT). The vitexin/ICG liposome was fabricated via LOC and its physicochemical property and release in vitro were evaluated. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and live/dead staining were used to examine the enhanced antitumor effect of vitexin/ICG liposome in cooperation with PDT/PTT, while the related mechanism was explored by flow cytometry and western blot. The results were as follows: (1) The prepared vitexin/ICG liposome was smaller in size, homogenous in particle size distribution with significant low polydispersity index (PDI), and enhanced cumulative release in vitro. (2) We found that the formulated liposome presented strong cancer cell inhibition and suppression of its migration in a dose-dependent manner. (3) Further mechanistic studies showed that liposome combined with near-infrared irradiation could significantly upregulate levels of B cell lymphoma 2-associated X (Bax) protein and decrease B cell lymphoma 2 (Bcl-2) at protein levels. The vitexin/ICG liposomes prepared based on a simple LOC platform can effectively enhance the solubility of insoluble drugs, and the combined effect of PTT/PDT can effectively increase their antitumor effect, which provides a simple and valid method for the clinical translation of liposomes.