Polyethyleneimine in designed nanocomposite based magnetic halloysite nanotubes for extraction and determination of gallic acid in green tea.

An innovative and simple nanocomposite denoted as MHNTs@PEI was synthesized for gallic acid (GA) analytical sample pretreatment. Polyethyleneimine (PEI) functionalized was binded onto magnetic halloysite nanotubes (MHNTs) to inhence adsorption capacity. MHNTs@PEI was obtained only through two steps modification (amination and PEI modification). Characterizations showed that there are layers of synthetic PEI on the tubular structure of the material and magnetic spheres on its surface, both indicating successful synthesis of the nanocomposite. Furthermore, the adsorption isotherms and kinetic modeling showed that the Langmuir model and pseudo-first-order model fit the adsorption data, respectively. MHNTs@PEI achieved an adsorption capacity of 158 mg·g-1. Overall, the abundant adsorption sites significantly improved the adsorption performance of the MHNTs@PEI. Regeneration tests demonstrated that the MHNTs@PEI exhibits effective adsorption, even after undergoing five consecutive cycles. Optimization of key parameters (ratio, volume of elution, elution time and frequency) in the process of adsorption and desorption was also conducted. The limit of detection (LOD) and that of the quantification (LOQ) were 0.19 and 0.63 µg·mL-1, respectively, and the recoveries were 95.67-99.43 %. Finally, the excellent magnetism (43.5 emu·g-1) and the adsorption feature of MHNTs@PEI enabled its successful utilization in analytical sample pretreatment through the extraction of GA from green tea.

Application of a three dimensional polyethyleneimine functionalized graphene oxide aerogel as an adsorbent for the determination of phytohormones in ginseng.

Aerogels have attracted considerable attention in sample pretreatment for their outstanding properties, such as the unique porous structure, large surface area and abundant modifiable active sites. The present research reports a three-dimensional interconnected porous network aerogel (PEI-AGO) manufactured based on graphene oxide (GO), polyethyleneimine (PEI) and agar as basic materials through a vacuum freeze-drying treatment. The PEI-AGO aerogel exhibits great potential as a solid phase extraction adsorbent for the selective purification of six endogenous plant hormones in conjunction with high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS). Several factors affecting the extraction efficiency were investigated. Under the optimized extraction conditions, a wide linear range of 0.5-100 ng mL-1 with a good linearity (r > 0.9934) was observed. Low limits of detection (LODs) and limits of quantification (LOQs) were obtained in the range of 0.032-0.155 ng mL-1 and 0.107-0.518 ng mL-1, respectively. Furthermore, the relative recoveries for spiked ginseng samples exhibited remarkable consistency, ranging from 90.2% to 117.6%, with a relative standard deviation (RSD) of ≤9.4% (n = 3). In summary, PEI-AGO has proven to be an effective adsorbent for the pretreatment and enrichment of phytohormones which can be used for the determination of trace endogenous acidic plant hormones in ginseng leaves.

Abatement of some commercial fungicide content from model dispersions by a new thiourea-graft-polyethyleneimine derivative.

A new derivative of polyethyleneimine (PEI) with 9% degree of substitution of its primary and secondary amino groups with thiourea moieties (TU9-PEI) has been synthesized and investigated as flocculant in model suspensions of commercial fungicide formulations Dithane M45, Melody Compact 49 WG, Cabrio®Top, and their mixtures. The structure of TU9-PEI, obtained by an aqueous one-pot strategy involving formaldehyde mediated coupling of PEI and TU, was confirmed by FTIR and 1H NMR spectroscopy as well as the streaming potential measurements. The settling time, polymer dose, and fungicide type and concentration were the parameters used for assessing the flocculation ability of the new polycation sample. The UV-Vis spectroscopy measurements revealed a good removal efficiency of TU9-PEI for all of the fungicides investigated, between 88 and 94%. Slightly higher removal percent was found for greater fungicide concentrations. The charge neutralization was indicated by zeta potential measurements (values close to zero recorded at the optimum polymer dose) as the main mechanism which contributed to the Dithane and Cabrio®Top particle removal and a combined effect of the TU9-PEI/fungicide particle electrostatic attractions and hydrogen bonds between both the amine and thiourea groups of the polycation chains and the hydroxyl ones on the copper oxychloride particles (negative values) in case of the Melody Compact 49 WG particle separation. Particle size and surface morphology analysis data gave supplementary evidences regarding the TU9-PEI ability to separate the fungicides investigated from simulated wastewater.

Xylanase covalent binding onto amidated pectin beads: Optimization, thermal, operational and storage stability studies and application.

Amidated pectin-polyethylene imine-glutaraldehyde (AP-PEI-GA) immobilizer was prepared. The ideal protocol that should be adopted during the immobilizer preparation was investigated via Box-Behnken design (BBD), and it comprised processing the AP beads with 3.4 % (w/w) PEI solution of pH 9.65 followed by 5.96 % (v/v) GA solution. The obtained AP-PEI-GA immobilizer was efficient, and it acquired 3.03 U.g-1 of immobilized xylanase (im-xylanase) activity. The computed Km and Vmax values for AP-PEI-GA im-xylanase were 16.67 mg.ml-1 and 20 g.ml-1.min-1, respectively. Through covalent coupling to AP-PEI-GA, Aspergillus niger xylanase thermodynamic properties T1/2 and D-values were increased by 2.05, 3.08, and 1.35 at 40, 50, and 60 °C, respectively. ΔHd and ΔGd for AP-PEI-GA im-xylanase at 40, 50, and 60 °C were higher than those for free form emphasizing more resistance to thermal denaturation. Im-xylanase showed 100 % activity for 20 successive cycles and hydrolyzed different agro-industrial wastes into reducing sugar and xylooligosaccharides (XOS) with more efficiency on pea peel (PP). AP-PEI-GA im-xylanase, PP weight, and hydrolysis time that should be adopted to obtain the highest reducing sugar and XOS yield were optimized through central composite design (CCD). Extracted XOS showed prebiotic and anti-oxidant activities.

Polyethyleneimine incorporated chitosan/α-MnO2 nanorod honeycomb-like composite foams with remarkable elasticity and ultralight property for the effective removal of U(VI) from aqueous solution.

The development of new adsorbents is needed to address the environmental challenges of radioactive wastewater treatment. Herein we reported a novel polyethyleneimine incorporated chitosan/α-MnO2 nanorod honeycomb-like composite (PCM) foam with remarkable elasticity and ultralight property for U(VI) removal. Among different PCM sorbents, PCM-40 possessed the highest sorption capacity for U(VI) due to its highly developed macroporous structure and high content of amine/imine groups. The kinetics were well-simulated by the pseudo-second-order model, indicating chemisorption as the rate-controlling step. The isotherms could be described by the Langmuir model, suggesting mono-layer homogeneous sorption of U(VI). The maximum sorption U(VI) capacity for PCM-40 reaches up to 301.9 mg/g at pH 4.5 and 298 K. The thermodynamic parameters revealed the spontaneous and endothermic nature of the adsorption process. The main sorption mechanism is related to the complexation of uranyl ions with the amine/imine and hydroxyl groups. The high sorption capacity, fast kinetic rate and relatively good selectivity of PCM-40 highlights its promising application in radioactive pollution cleanup.

MicroSPECT Imaging-Guided Treatment of Idiopathic Pulmonary Fibrosis in Mice with a Vimentin-Targeting 99mTc-Labeled N-Acetylglucosamine-Polyethyleneimine.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with poor prognosis. Evidence has shown that vimentin is a key regulator of lung fibrogenesis. 99mTc-labeled N-acetylglucosamine-polyethyleneimine (NAG-PEI), a vimentin-targeting radiotracer, was used for the early diagnosis of IPF, and NAG-PEI was also used as a therapeutic small interfering RNA (siRNA) delivery vector for the treatment of IPF in this study. Single-photon emission-computed tomography (SPECT) imaging of bleomycin (BM)- and silica-induced IPF mice with 99mTc-labeled NAG-PEI was performed to visualize pulmonary fibrosis and monitor the treatment efficiency of siRNA-loaded NAG-PEI, lipopolysaccharide (LPS, a tolerogenic adjuvant), or zymosan (ZYM, an immunostimulant). The lung uptakes of 99mTc-NAG-PEI in the BM- and silica-induced IPF mice were clearly and directly correlated with IPF progression. The lung uptake of 99mTc-NAG-PEI in the NAG-PEI/TGF-ß1-siRNA treatment group or LPS treatment group was evidently lower than that in the control group, while the lung uptake of 99mTc-NAG-PEI was significantly higher in the ZYM treatment group compared to that in the control group. These results demonstrate that NAG-PEI is a potent MicroSPECT imaging-guided theranostic platform for IPF diagnosis and therapy.

A Universal and Reversible Wet Adhesive via Straightforward Aqueous Self-Assembly of Polyethylenimine and Polyoxometalate.

The excellent adhesion of mussels under wet conditions has inspired the development of numerous catechol-based wet adhesives. Nevertheless, the performance of catechol-based wet adhesive suffers from the sensitivity toward temperature, pH, or oxidation stimuli. Therefore, it is of great significance to develop non-catechol-based wet adhesives to fully recapitulate nature's dynamic function. Herein, a novel type of non-catechol-based wet adhesive is reported, which is readily formed by self-assembly of commercially available branched polyethylenimine and phosphotungstic acid in aqueous solution through the combination of electrostatic interaction and hydrogen bonding. This wet adhesive shows reversible, tunable, and strong adhesion on diverse substrates and further exhibits high efficacy in promoting biological wound healing. During the healing of the wound, the as-prepared wet adhesive also possesses inherent antimicrobial properties, thus avoiding inflammations and infections due to microorganism accumulation.

Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues.

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes' pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-ß/collagen, Wnt/ß-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.

Amplified electrochemical antibiotic aptasensing based on electrochemically deposited AuNPs coordinated with PEI-functionalized Fe-based metal-organic framework.

A facile and versatile competitive electrochemical aptasensor for tobramycin (TOB) detection is described using electrochemical-deposited AuNPs coordinated with PEI-functionalized Fe-based metal-organic framework (AuNPs/P-MOF) as signal-amplification platform and a DNA probe labeled with methylene blue (MB) at the 3'-end (MB-Probe) as a signal producer. First, F-Probe (short complementary DNA strands of both the aptamer and the MB-Probe label with a sulfhydryl group at the 5'-end) was immobilized on the AuNPs/P-MOF modified electrode as detection probes, which competed with TOB in binding to the aptamer. TOB-aptamer binding resulted in F-Probe remaining unhybridized on the electrode surface, so that a significant current response was generated by hybridizing with MB-Probe instead. The developed strategy showed favorable repeatability, with a relative standard deviation (RSD) of 4.3% computed over five independent assays, and high stability, with only 6.8% degradation after 15 days of storage. Under optimal conditions, the proposed aptamer strategy exhibited a linear detection range from 100 pM to 500 nM with a limit of detection (LOD) of 56 pM (S/N = 3). The electrochemical aptasensor demonstrated remarkable selectivity, and its feasibility for accurate and quantitative detection of TOB in milk samples was confirmed (RSD < 4.5%). Due to its simple design, easy operation, and high sensitivity and selectivity, the proposed method could expect to detect other antibiotics by replacing the aptamers. In summary, this study provides a simple and effective new strategy for electrochemical aptasening based on MOF-based sensing interface. Scheme illustration of label-free competitive electrochemical aptamer-based detection of tobramycin based on electrochemically deposited AuNPs coordinated with PEI-functionalized Fe-based metal-organic framework as signal-amplification platform.

[Preparation of branched polyethyleneimine-assisted boric acid-functionalized magnetic nanoparticles and its application to selective enrichment of ginsenoside Re].

Panax ginseng has a 5000-year-long history as a traditional herbal medicine in Eastern Asia and North America. It is also known as crown jewel in traditional Chinese herbs because of its wide pharmacological properties. Ginsenosides, a class of saponins containing triterpene aglycones and various sugar moieties, are the main active components of ginseng. Considering the low abundance of ginsenosides and other abundant interferences, separation of ginsenosides is essential prior to further analysis. Recently, our group demonstrated the potential of a boronate affinity material for the selective enrichment of ginsenosides. However, conventional boronate affinity materials suffer from an apparent drawback. The binding strength of boronic acids toward cis-diol-containing compounds is low, with dissociation constants (Kd) ranging from 10-1 to 10-3mol/L. Thus, it is necessary to develop boronate affinity materials with high binding strength. In this study, we developed polyethyleneimine (PEI)-functionalized boronate affinity magnetic nanoparticles (BA-MNPs) for the selective enrichment of ginsenosides. Branched PEI was applied as a scaffold to amplify the number of boronic acid moieties, while 3-formylphenylboronic acid, which shows high affinity toward cis-diol-containing molecules, was used as the affinity ligand. In addition, the presence of the multi-glycan structure of ginsenoside leads to higher binding affinity between the PEI-BA-MNPs due to the synergistic multivalent binding effect. Combining with high performance liquid chromatography, a method for the selective analysis of ginsenosides was established. With ginsenoside Re as the representative and under the optimized conditions for magnetic solid-phase extraction, the developed method showed good linearity in the range of 50-800 µg/L, with a linear correlation coefficient (R2) of 0.9681. At different spiked levels (0.1-10 mg/L), the recoveries were in the range of 91.5%-117.3%, and the relative standard deviations (RSDs) ranged from 7.2% to 13.4%. Since the PEI-BA-MNPs exhibited significantly improved binding strength toward ginsenosides, they could extract trace glycoproteins. After enrichment, a 50-fold improvement in the sensitivity was achieved. In addition, the PEI-BA-MNPs maintained at least 72% of their original binding capacity after five consecutive uses. Finally, the developed method was applied to the determination of ginsenoside Re in commercial medicine (Qipi oral liquid). As opposed to the tedious and time-consuming sample preparation in the standard method (Pharmacopoeia of the People's Republic of China, 2015; ChP2015), the present protocol allowed for direct enrichment of the diluted commercial medicine with PEI-BA-MNPs. The magnetic separation made the overall experiment much simpler than the standard ChP2015 method. After washing and elution, the enriched ginsenoside Re was eluted and subjected to HPLC-UV analysis. The results obtained with the developed method (0.27%) were similar to those of ChP2015 (0.31%). We have experimentally demonstrated that PEI-BA-MNPs are ideal affinity sorbents for the selective enrichment of ginsenosides owing to their significant advantages, including high affinity, excellent selectivity, easy manipulation, high binding capacity, and fast binding equilibrium. As many saponins contain sugar side chains, we foresee a promising prospect for the proposed method in real-world applications.

PEG-PEI-modified gated N-doped mesoporous carbon nanospheres for pH/NIR light-triggered drug release and cancer phototherapy.

A novel hybrid drug carrier has been designed, taking N-doped mesoporous carbon (NMCS) as the core and PEG-PEI as the outer shell. NMCS was functionalized with a photocleavable nitrobenzyl-based linker following a click reaction. Gemcitabine was loaded into NMCS prior to the functionalization via π-π stacking interactions. NIR and the pH-responsive behavior of NMCS-linker-PEG-PEI bestow the multifunctional drug carrier with the controlled release of gemcitabine triggered by dual stimuli. The NMCS core upconverts NIR light to UV, which is absorbed by a photosensitive molecular gate and results in its cleavage and drug release. Further, NMCS converts NIR to heat, which deforms the outside polymer shell, thus triggering the drug release process. The release can be promptly arrested if the NIR source is switched off. A promising gemcitabine release of 75% has been achieved within 24 h under the dual stimuli of pH and temperature. NMCS-linker-PEG-PEI produced reactive oxygen species (ROS), which were verified in FaDu cells using flow cytometry. In vitro experiments showed that the NMCS-linker-PEG-PEI-GEM hybrid particle can induce synergistic therapeutic effects in FADU cells when exposed to the NIR light.

TiO2@HNTs Robustly Decorated PVDF Membrane Prepared by a Bioinspired Accurate-Deposition Strategy for Complex Corrosive Wastewater Treatment.

As industrialization has spread all around the world, the problems of water pollution such as offshore oil spill and industrial sewage discharge have spread with it. Although many new separation materials have been successfully developed to deal with this crisis, a large number of water treatment materials only focus on the treatment of classified single water pollutant under mild conditions. It is a great challenge to treat soluble contaminants such as water-soluble dyes and insoluble contaminants, for example, emulsified oils simultaneously in a strong corrosive environment. Herein, in this work, corrosive resistance and multifunctional surface on a commercial polyvinylidene difluoride (PVDF) membrane via a tunicate-inspired gallic acid-assisted accurate-deposition strategy is created. Owing to the titanium-carboxylic coordination bonding and accurate-deposition strategy, the as-prepared membrane exhibits extraordinary stability, facing various harsh environmental challenges and incredibly corrosive situations (e.g., 4 M NaOH, 4 M HCl, and saturated NaCl solution). The robust multifunctional surface also endows commercial PVDF membrane with the ability for in situ separation and adsorption of surfactant-stabilized oil-in-water (corrosive and dyed) emulsions with high adsorption efficiencies up to 99.9%, separation efficiencies above 99.6%, and permeation flux as high as 15,698 ± 211 L/(m2·h·bar). Furthermore, the resultant membrane can be regenerated facilely and rapidly by flushing a small amount of HCl (4 M) or NaOH (4 M), making the corrosive resistance membrane attain a long-term and high-efficiency application for complex dyed wastewater treatment. Therefore, the multifunctional membrane has a broad application prospect in the industrial field.

Dopamine-polyethyleneimine co-deposition cellulose filter paper for α-Glucosidase immobilization and enzyme inhibitor screening.

In this work, cellulose filter paper (CFP), which is inexpensive and commercially available, was used as the carrier, and the immobilized α-glucosidase was obtained by two steps: firstly, the surface of CFP was modified by polydopamine/polyethyleneimine (PDA/PEI) co-deposition method to obtain CFP-PDA/PEI with a uniform coating of rich positive charge; subsequently, α-glucosidase was immobilized on the CFP-PDA/PEI by electrostatic adsorption. The free enzyme and immobilized enzyme have the same optimal temperature (70℃) and pH (8.0), and their Km is similar, which is 2.2 and 2.8, respectively. These results show that the immobilization process does not change the properties of the enzyme greatly. The immobilized enzyme still maintains 75.6% of its initial activity after 10 repeated uses, showing good reusability. The excellent repeatability (RSD = 2.2%, n = 5) and the verification of competitive inhibitor (acarbose) illustrates the reliability of the immobilized enzymes for enzyme inhibitor screening. Finally, combined with CE, a screening method based immobilized α-glucosidase was proposed and applied to screen the α-glucosidase inhibitory from 10 kinds of Traditional Chinese medicines (TCMs) in vitro. The results indicated that the method was a very effective tool for screening potential α-glucosidase inhibitors from TCMs.

ICG/5-Fu coencapsulated temperature stimulus response nanogel drug delivery platform for chemo-photothermal/photodynamic synergetic therapy.

The multiple diagnosis and treatment mechanisms of chemotherapy combined with photothermal/photodynamic therapy have very large application prospects in the field of cancer treatment. Therefore, in order to achieve effective and safe antitumour treatment, it is necessary to design an intelligent responsive polymer nanoplatform as a drug delivery system. Herein, the thermosensitive poly-N-isopropylacrylamide (PNIPAM) nanogel particles were prepared by soap-free emulsion polymerization and loaded with a large amount of photosensitizer indocyanine green (ICG) and anticarcinogen 5-fluorouracil (5-Fu), which effectively to realize the cooperative chemotherapy and photothermal/photodynamic therapy for tumours. The 5-Fu@ICG-PNIPAM nanogels significantly improved the bioavailability of the drug and achieved controlled release. In addition, under near-infrared laser (NIR) irradiation at 808 nm, 5-Fu@ICG-PNIPAM nanogels generated lots of heat and reactive oxygen, which significantly enhanced cellular uptake and in vitro antitumour treatment effects. The results showed that 5-Fu@ICG-PNIPAM nanogels were effectively endocytosed by HeLa cells, which also enhanced the drug's entrance into the nucleus. Moreover, compared with alone chemotherapy or photothermal/photodynamic therapy, 5-Fu@ICG-PNIPAM nanogels significantly increased cytotoxicity under NIR irradiation, suggesting that chemotherapy and photothermal/photodynamic synergistic therapy had excellent antitumour properties. Therefore, this temperature-responsive nanogel platform probably has great application prospects in clinical antitumour treatment.

Non-viral strategies for delivering genome editing enzymes.

Genome-editing tools such as Cre recombinase (Cre), zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and most recently the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein system have revolutionized biomedical research, agriculture, microbial engineering, and therapeutic development. Direct delivery of genome editing enzymes, as opposed to their corresponding DNA and mRNA precursors, is advantageous since they do not require transcription and/or translation. In addition, prolonged overexpression is a problem when delivering viral vector or plasmid DNA which is bypassed when delivering whole proteins. This lowers the risk of insertional mutagenesis and makes for relatively easier manufacturing. However, a major limitation of utilizing genome editing proteins in vivo is their low delivery efficiency, and currently the most successful strategy involves using potentially immunogenic viral vectors. This lack of safe and effective non-viral delivery systems is still a big hurdle for the clinical translation of such enzymes. This review discusses the challenges of non-viral delivery strategies of widely used genome editing enzymes, including Cre recombinase, ZFNs and TALENs, CRISPR/Cas9, and Cas12a (Cpf1) in their protein format and highlights recent innovations of non-viral delivery strategies which have the potential to overcome current delivery limitations and advance the clinical translation of genome editing.

Silencing of Gasdermin D by siRNA-Loaded PEI-Chol Lipopolymers Potently Relieves Acute Gouty Arthritis through Inhibiting Pyroptosis.

Gasdermin D (GSDMD) plays a causal role in NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis eruption, which has been regarded as a potential therapeutic target for pyroptosis-related diseases including acute gouty arthritis. In the present study, the synthesized PEI-Chol (cholesterol grafted polyethylenimine) was assembled with GSDMD small interfering RNA (siRNA) to form PEI-Chol/siGSDMD polyplexes, which provided high transfection efficiency for siRNA-mediated GSDMD knockdown. Then we evaluated the effect of GSDMD siRNA-loaded PEI-Chol on inflammatory cascades in bone-marrow-derived macrophages (BMDMs) and acute gouty arthritis animal models under MSU exposure. When accompanied by pyroptosis blockade and decreased release of interleukin-1 beta (IL-1ß), NLRP3 inflammasome activation was also suppressed by GSDMD knockdown in vivo and in vitro. Moreover, in MSU-induced acute gouty arthritis mice, blocking GSDMD with siRNA significantly improved ankle swelling and inflammatory infiltration observed in histopathological analysis. Furthermore, investigation using a mouse air pouch model verified the effect of siGSDMD-loaded PEI-Chol on pyroptosis of recruited macrophages and related signaling pathways in response to MSU. These novel findings exhibited that GSDMD knockdown relieved acute gouty arthritis through inhibiting pyroptosis, providing a possible therapeutic approach for MSU-induced acute gouty arthritis molecular therapy using PEI-Chol as a nucleic acid delivery carrier.

Mitochondria-targeting NO gas nanogenerator for augmenting mild photothermal therapy in the NIR-II biowindow.

An intelligent nitric oxide gas-releasing nanoplatform based on CuS-nanoplates has been designed to overcome the heat endurance of tumor cells by the inhibition of HSP90 expression with the released NO gas in mitochondria and thereby realize enhanced PTT under mild temperature conditions.

Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer.

BACKGROUND: Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer. METHODS: Firstly, CM-ß-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model. RESULTS: T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 µg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model. CONCLUSION: The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.

Calcium based siRNA coating: a novel approach for knockdown of HER2 gene in MCF-7 cells using gold nanoparticles.

Surface functionalization of nanoparticles (NPs) for therapeutic siRNA delivery into cancer cells has gained interest. The present study was designed for surface functionalization of gold nanoparticles (AuNPs) for efficient siRNA delivery and knockdown in cancer cells. In order to achieve this objective, AuNPs were coated with HER2-siRNA in the presence of 11-mercaptoundecanoic acid (11-MUA), calcium chloride (CaCl2) and polyethyleneimine (PEI) in alternate charge bearing successive layers. MCF-7 cells were cultured and transfected with fabricated assembly of AuNPs. Cytotoxicity analysis revealed that the half inhibitory concentration (IC50) for the formulation was 45.35 nM  . Total RNA was isolated from transfected cells, reverse transcribed into complementary DNA (cDNA) and real-time polymerase chain reaction (RT-PCR) was performed. The RT-PCR based delta-delta Ct analysis in treated cells revealed a significant 18.94 times decrease (p<0.001) in the expression of HER2 gene standardized with ACTB housekeeping gene as compared to untreated cells, which makes this formulation a potent approach for siRNA delivery and  gene knockout.

A novel multifunctional FePt/BP nanoplatform for synergistic photothermal/photodynamic/chemodynamic cancer therapies and photothermally-enhanced immunotherapy.

A new multi-modal therapy agent, FePt/BP-PEI-FA nanoplatform, with FePt nanoparticles (FePt NPs) loaded onto ultrathin black phosphorus nanosheets (BPNs), has been constructed to enhance synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) that target primary tumors. In this work, BPNs exhibit excellent photothermal and photodynamic behaviors under different wavelength laser irradiation. After polyethylenimine (PEI) modification, FePt NPs with sizes of 3-4 nm are uniformly attached onto the surface of modified BPNs via electrostatic adsorption. FePt NPs, as a ferroptosis agent, can transform endogenous H2O2 into reactive oxygen species (ROS) through the Fenton reaction, ultimately inducing cell death. Based on magnetic resonance imaging (MR) and thermal imaging, the as-prepared FePt/BP-PEI-FA NCs can inhibit tumor growth by achieving synergistic therapies. More significantly, combined with cytotoxic T lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade, FePt/BP-PEI-FA NC-induced PTT can control both primary and untreated distant tumors' growth. Therefore, FePt/BP-PEI-FA NCs is a potential multifunctional nanoagent for effective anti-tumor applications.