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1.
Biosensors (Basel) ; 14(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38667154

RESUMO

We designed and optimized a glucose biosensor system based on a screen-printed electrode modified with the NAD-GDH enzyme. To enhance the electroactive surface area and improve the electron transfer efficiency, we introduced graphene oxide (GO) and ferrocene-modified linear poly(ethylenimine) (LPEI-Fc) onto the biosensor surface. This strategic modification exploits the electrostatic interaction between graphene oxide, which possesses a negative charge, and LPEI-Fc, which is positively charged. This interaction results in increased catalytic current during glucose oxidation and helps improve the overall glucose detection sensitivity by amperometry. We integrated the developed glucose sensor into a flow injection (FI) system. This integration facilitates a swift and reproducible detection of glucose, and it also mitigates the risk of contamination during the analyses. The incorporation of an FI system improves the efficiency of the biosensor, ensuring precise and reliable results in a short time. The proposed sensor was operated at a constant applied potential of 0.35 V. After optimizing the system, a linear calibration curve was obtained for the concentration range of 1.0-40 mM (R2 = 0.986). The FI system was successfully applied to determine the glucose content of a commercial sports drink.


Assuntos
Técnicas Biossensoriais , Compostos Ferrosos , Glucose , Grafite , Metalocenos , Polietilenoimina , Grafite/química , Metalocenos/química , Compostos Ferrosos/química , Polietilenoimina/química , Glucose/análise , Eletrodos , Oxirredução
2.
AAPS PharmSciTech ; 25(4): 83, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605211

RESUMO

Smart nanomedicinal treatment for cancer manifests a solubility challenge with inherent nanoscale size and nonspecific release with stimuli-responsive potential. This is the limelight in novel chemotherapy to pursue physiochemical differences between the tumor microenvironment (TME) and normal cells, which introduces active groups of nanocarriers responding to various stimuli, endowing them with concise responses to various tumor-related signals. The nanogels were successfully prepared by a modified solvent evaporation technique. Nine batches were formulated by changing the chitosan concentration (12, 14, 16 mg/ml) and sonication time (5, 10, 15 min). The formulations were optimized for particle size and zeta potential with high percent entrapment efficiency (%EE) through Central Composite Design software. The optimized batch F7 had a 182-nm size and high zeta potential (64.5 mV) with 98% EE. The drug release of F7 was higher at pH 6 (97.556%) than at pH 7.4 (45.113%). The pharmacokinetic study shows that the release follows the Hixon plot model (R2 = 0.9334) that shifts to zero order (R2 = 0.9149). The nanogel F7 was observed for stability and showed an absence of color change, phase separation, and opacity for 6 months. In the present study, the pH difference between cancer cells and normal cells is the key point of the smart nanogel. This study is promising but challenging depending on the in vivo study. The nanogel was successfully prepared and evaluated for pH-responsive release. As hemangiosarcoma commonly occurs in dogs, this formulation helps to limit the difficulties with administration.


Assuntos
Hemangiossarcoma , Polietilenoglicóis , Polietilenoimina , Polímeros , Animais , Cães , Nanogéis , Sorafenibe , Concentração de Íons de Hidrogênio , Portadores de Fármacos , Microambiente Tumoral
3.
BMC Vet Res ; 20(1): 127, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561720

RESUMO

BACKGROUND: Pseudomonas putida is a pathogenic bacterium that induces great losses in fishes, including Nile tilapia (Oreochromis niloticus). Currently, the application of nanomaterials in aquaculture practices has gained more success as it endows promising results in therapies compared to traditional protocols. OBJECTIVE: Therefore, the current perspective is considered the first report to assess the anti-bacterial efficacy of titanium dioxide nanogel (TDNG) against Pseudomonas putida (P. putida) in Nile tilapia. METHODS: The fish (n = 200; average body weight: 47.50±1.32 g) were allocated into four random groups (control, TDNG, P. putida, and TDNG + P. putida), where 0.9 mg/L of TDNG was applied as bath treatment for ten days. RESULTS: Outcomes revealed that P. putida infection caused ethological alterations (surfacing, abnormal movement, and aggression) and depression of immune-antioxidant variables (complement 3, lysozyme activity, total antioxidant capacity, superoxide dismutase, and reduced glutathione content). Additionally, a substantial elevation in hepatorenal biomarkers (aspartate and alanine aminotransferases and creatinine) with clear histopathological changes and immuno-histochemical alterations (very weak BCL-2 and potent caspase-3 immuno-expressions) were seen. Surprisingly, treating P. putida-infected fish with TDNG improved these variables and obvious restoration of the tissue architectures. CONCLUSION: Overall, this report encompasses the key role of TDNG as an anti-bacterial agent for controlling P. putida infection and improving the health status of Nile tilapia.


Assuntos
Ciclídeos , Doenças dos Peixes , Polietilenoglicóis , Polietilenoimina , Pseudomonas putida , Titânio , Animais , Antioxidantes , Nanogéis , Dieta , Suplementos Nutricionais , Ração Animal/análise , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/microbiologia
4.
BMC Complement Med Ther ; 24(1): 138, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566054

RESUMO

Herbal components are highly useful assets for the advancement of novel antibacterial drugs. Nanotechnology holds great promise as an approach to enhance the effectiveness and develop the composition of these substances. The study developed nanogels incorporating camphor, thymol, and a combination derived from the initial nanoemulsions with particle sizes of 103, 85, and 135 nm, respectively. The viscosity of nanogels and the successful loading of compounds in them were examined by viscometery and ATR-FTIR studies. The bactericidal properties of the nanogels were examined against four bacterial strains. The nanogel containing camphor and thymol at 1250 µg/mL concentration exhibited complete growth suppression against Pseudomonas aeruginosa and Staphylococcus aureus. The thymol nanogel at 1250 µg/mL and the camphor nanogel at 2500 µg/mL exhibited complete inhibition of growth on Listeria monocytogenes and Escherichia coli, respectively. Both nanogels showed favorable effectiveness as antibacterial agents and could potentially examine a wide range of pathogens and in vivo studies.


Assuntos
Cânfora , Polietilenoglicóis , Polietilenoimina , Timol , Timol/farmacologia , Nanogéis , Cânfora/farmacologia , Antibacterianos/farmacologia , Escherichia coli
5.
Urolithiasis ; 52(1): 52, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564033

RESUMO

Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters' excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations.


Assuntos
Cymbopogon , Água Potável , Cálculos Renais , Polietilenoglicóis , Polietilenoimina , Urolitíase , Animais , Ratos , Petroselinum , Cloreto de Amônio , Goma Arábica , Emulsões , Catalase , Magnésio , Nanogéis , Urolitíase/induzido quimicamente , Urolitíase/tratamento farmacológico , Urolitíase/prevenção & controle , Sementes , Antioxidantes/uso terapêutico , Etanol , Glutationa , Oxalatos , Etilenoglicóis , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
6.
J Mater Chem B ; 12(16): 3927-3946, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38563779

RESUMO

Messenger RNA (mRNA) based vaccines have been introduced worldwide to combat the Covid-19 pandemic. These vaccines consist of non-amplifying mRNA formulated in lipid nanoparticles (LNPs). Consequently, LNPs are considered benchmark non-viral carriers for nucleic acid delivery. However, the formulation and manufacturing of these mRNA-LNP nanoparticles are expensive and time-consuming. Therefore, we used self-amplifying mRNA (saRNA) and synthesized novel polymers as alternative non-viral carrier platform to LNPs, which enable a simple, rapid, one-pot formulation of saRNA-polyplexes. Our novel polymer-based carrier platform consists of randomly concatenated ethylenimine and propylenimine comonomers, resulting in linear, poly(ethylenimine-ran-propylenimine) (L-PEIx-ran-PPIy) copolymers with controllable degrees of polymerization. Here we demonstrate in multiple cell lines, that our saRNA-polyplexes show comparable to higher in vitro saRNA transfection efficiencies and higher cell viabilities compared to formulations with Lipofectamine MessengerMAX™ (LFMM), a commercial, lipid-based carrier considered to be the in vitro gold standard carrier. This is especially true for our in vitro best performing saRNA-polyplexes with N/P 5, which are characterised with a size below 100 nm, a positive zeta potential, a near 100% encapsulation efficiency, a high retention capacity and the ability to protect the saRNA from degradation mediated by RNase A. Furthermore, an ex vivo hemolysis assay with pig red blood cells demonstrated that the saRNA-polyplexes exhibit negligible hemolytic activity. Finally, a bioluminescence-based in vivo study was performed over a 35-day period, and showed that the polymers result in a higher and prolonged bioluminescent signal compared to naked saRNA and L-PEI based polyplexes. Moreover, the polymers show different expression profiles compared to those of LNPs, with one of our new polymers (L-PPI250) demonstrating a higher sustained expression for at least 35 days after injection.


Assuntos
Polietilenoimina , RNA Mensageiro , Transfecção , Animais , Transfecção/métodos , Polietilenoimina/química , Humanos , RNA Mensageiro/genética , Camundongos , Polipropilenos/química , Polímeros/química , Portadores de Fármacos/química , SARS-CoV-2/efeitos dos fármacos , Nanopartículas/química
7.
Mikrochim Acta ; 191(5): 282, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652326

RESUMO

A novel dual-mode fluorometric and colorimetric sensing platform is reported for determining glutathione S-transferase (GST) by utilizing polyethyleneimine-capped silver nanoclusters (PEI-AgNCs) and cobalt-manganese oxide nanosheets (CoMn-ONSs) with oxidase-like activity. Abundant active oxygen species (O2•-) can be produced through the CoMn-ONSs interacting with dissolved oxygen. Afterward, the pink oxDPD was generated through the oxidation of colorless N,N-diethyl-p-phenylenediamine (DPD) by O2•-, and two absorption peaks at 510 and 551 nm could be observed. Simultaneously, oxDPD could quench the fluorescence of PEI-AgNCs at 504 nm via the inner filter effect (IFE). However, in the presence of glutathione (GSH), GSH prevents the oxidation of DPD due to the reducibility of GSH, leading to the absorbance decrease at 510 and 551 nm. Furthermore, the fluorescence at 504 nm was restored due to the quenching effect of oxDPD on decreased PEI-AgNCs. Under the catalysis of GST, GSH and1-chloro-2,4-dinitrobenzo (CDNB) conjugate to generate an adduct, initiating the occurrence of the oxidation of the chromogenic substrate DPD, thereby inducing a distinct colorimetric response again and the significant quenching of PEI-AgNCs. The detection limits for GST determination were 0.04 and 0.21 U/L for fluorometric and colorimetric modes, respectively. The sensing platform illustrated reliable applicability in detecting GST in real samples.


Assuntos
Cobalto , Colorimetria , Glutationa Transferase , Compostos de Manganês , Nanopartículas Metálicas , Óxidos , Polietilenoimina , Prata , Polietilenoimina/química , Prata/química , Cobalto/química , Óxidos/química , Compostos de Manganês/química , Nanopartículas Metálicas/química , Colorimetria/métodos , Glutationa Transferase/metabolismo , Glutationa Transferase/química , Limite de Detecção , Oxirredutases/química , Oxirredutases/metabolismo , Humanos , Glutationa/química , Oxirredução , Técnicas Biossensoriais/métodos , Fenilenodiaminas/química , Nanoestruturas/química
8.
Sensors (Basel) ; 24(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38610380

RESUMO

Environmental monitoring and the detection of antibiotic contaminants require expensive and time-consuming techniques. To overcome these challenges, gold nanoparticle-mediated fluorometric "turn-on" detection of Polymyxin B (PMB) in an aqueous medium was undertaken. The molecular weight of polyethyleneimine (PEI)-dependent physicochemical tuning of gold nanoparticles (PEI@AuNPs) was achieved and employed for the same. The three variable molecular weights of branched polyethyleneimine (MW 750, 60, and 1.3 kDa) molecules controlled the nano-geometry of the gold nanoparticles along with enhanced stabilization at room temperature. The synthesized gold nanoparticles were characterized through various advanced techniques. The results revealed that polyethyleneimine-stabilized gold nanoparticles (PEI@AuNP-1-3) were 4.5, 7.0, and 52.5 nm in size with spherical shapes, and the zeta potential values were 29.9, 22.5, and 16.6 mV, respectively. Accordingly, the PEI@AuNPs probes demonstrated high sensitivity and selectivity, with a linear relationship curve over a concentration range of 1-6 µM for polymyxin B. The limit of detection (LOD) was calculated as 8.5 nM. This is the first unique report of gold nanoparticle nano-geometry-dependent FRET-based turn-on detection of PMB in an aqueous medium. We believe that this approach would offer a complementary strategy for the development of a highly sophisticated and advanced sensing system for PMB and act as a template for the development of new nanomaterial-based engineered sensors for rapid antibiotic detection in environmental as well as biological samples.


Assuntos
Nanopartículas Metálicas , Polimixina B , Ouro , Peso Molecular , Polietilenoimina , Transferência Ressonante de Energia de Fluorescência , Antibacterianos
9.
Soft Matter ; 20(16): 3499-3507, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38595066

RESUMO

Polymeric vesicles are perspective vehicles for fabricating enzymatic nanoreactors towards diverse biomedical and catalytic applications, yet the design of stable and permeable vesicles remains challenging. Herein, we developed polyion complex (PIC) vesicles featuring high stability and a permeable membrane for adequate enzyme loading and activation. Our design relies on co-assembly of an anionic diblock copolymer (PSS96-b-PEO113) with cationic branched poly(ethylenimine) (PEI). The polymer combination endows strong electrostatic interaction between the PSS and PEI building blocks, so their assembly can be implemented at a high salt concentration (500 mM NaCl), under which the charge interaction of the enzyme-polymer is inhibited. This control realizes the successful and safe loading of enzymes associated with the formation of stable PIC vesicles with an intrinsic permeable membrane that is favourable for enhancing enzymatic activity. The control factors for vesicle formation and enzyme loading were investigated, and the general application of loading different enzymes for cascade reaction was validated as well. Our study reveals that proper design and combination of polyelectrolytes is a facile strategy for fabricating stable and permeable polymeric PIC vesicles, which exhibit clear advantages for loading and activating enzymes, consequently boosting their diverse applications as enzymatic nanoreactors.


Assuntos
Polietilenoimina , Polietilenoimina/química , Permeabilidade , Polímeros/química , Polieletrólitos/química
10.
Carbohydr Polym ; 332: 121935, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431402

RESUMO

A novel cellulose composite (denoted as PEI@MMA-1) with porous interconnected structure was prepared by adsorbing methyl cellulose (MC) onto microcrystalline cellulose (MCC) and cross-linking polyethyleneimine (PEI) with MCC by the action of epichlorohydrin, which had the excellent adsorption property, wettability and elasticity. The performances of PEI@MMA-1 composite for removing tetracycline (TC), Cu2+ and coexistent pollutant (TC and Cu2+ mixture) were systematically explored. For single TC or Cu2+ contaminant, the maximum adsorption capacities were 75.53 and 562.23 mg/g at 30 °C, respectively, while in the dual contaminant system, they would form complexes and Cu2+ could play a "bridge" role to remarkably promote the adsorption of TC with the maximum adsorption capacities of 281.66 and 253.58 mg/g for TC and Cu2+. In addition, the adsorption kinetics, isotherms and adsorption mechanisms of single-pollutant and dual-pollutant systems have been thoroughly investigated. Theoretical calculations indicated that the amide group of TC molecule with the assistance of Cu2+ interacted with the hydroxyl group of PEI@MMA-1 composite to enhance the TC adsorption capacity. Cycle regeneration and fixed bed column experiments revealed that the PEI@MMA-1 possessed the excellent stability and utility. Current PEI@MMA-1 cellulose composite exhibited a promising application for remediation of heavy metals and antibiotics coexistence wastewater.


Assuntos
Celulose/análogos & derivados , Cobre , Polietilenoimina/análogos & derivados , Poluentes Químicos da Água , Cobre/química , Adsorção , Poluentes Químicos da Água/química , Tetraciclina/química , Antibacterianos , Íons , Cinética
11.
Molecules ; 29(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38474444

RESUMO

Non-viral vectors have been developing in gene delivery due to their safety and low immunogenicity. But their transfection effect is usually very low, thus limiting the application. Hence, we designed eight peptides (compounds 1-8). We compared their performances; compound 8 had the best transfection efficacy and biocompatibility. The transfection effect was similar with that of PEI, a most-widely-employed commercial transfection reagent. Atomic force microscope (AFM) images showed that the compound could self-assemble and the self-assembled peptide might encapsulate DNA. Based on these results, we further analyzed the inhibitory result in cancer cells and found that compound 8 could partially fight against Hela cells. Therefore, the compound is promising to pave the way for the development of more effective and less toxic transfection vectors.


Assuntos
Neoplasias , Peptídeos , Humanos , Células HeLa , Transfecção , Peptídeos/química , Vetores Genéticos , DNA/química , Polietilenoimina/química
12.
Nanomedicine (Lond) ; 19(10): 895-914, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38530906

RESUMO

Aim: Osteoporosis is a systemic skeletal disorder characterized by reduced osteoblast differentiation, predominantly by overexpression of the Sost gene. A layer-by-layer approach enabled encapsulation of Sost siRNA to enhance the short half-life and poor transfection capacity of siRNA. Materials & methods: Polyethyleneimine and siRNA on chitosan-coated gold nanoparticles (PEI/siRNA/Cs-AuNPs) were engineered using chitosan-reduced gold nanoparticles. They were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared and gel-mobility assays. Detailed in vitro experiments, gene silencing and western blots were performed. Results: A total of 80% knockdown of the target sclerostin protein was observed by PEI/siRNA/Cs-AuNPs, q-PCR showed threefold downregulation of the Sost gene. Osteogenic markers RunX2 and Alp were significantly upregulated. Conclusion: We report a safe, biocompatible nanotherapeutic strategy to enhance siRNA protection and subsequent silencing to augment bone formation.


Assuntos
Quitosana , Nanopartículas Metálicas , Quitosana/química , Ouro , Nanopartículas Metálicas/química , Osteogênese/efeitos dos fármacos , Polietilenoimina/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Camundongos
13.
Int J Biol Macromol ; 265(Pt 2): 130969, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508562

RESUMO

Polyethyleneimine-modified magnetic sugarcane bagasse cellulose film (P-SBC/Fe3O4 film) was simply fabricated for the removal of ibuprofen (IBP), a typical emerging organic contaminant. The P-SBC/Fe3O4 film exhibited an equilibrium adsorption amount of 370.52 mg/g for IBP and a corresponding removal efficiency of 92.63 % under following adsorption conditions: 318 K, pH 4, and 0.25 mg/mL dosage. Thermodynamic studies indicated that adsorption of IBP on the P-SBC/Fe3O4 film was spontaneous (∆G < 0) and endothermic (∆H > 0). The adsorption data conformed to the Freundlich isotherm model and multilayer adsorption model (two layers), and an average of 3-4 active sites on the P-SBC/Fe3O4 film share an IBP molecule. Both the EDR-IDR and AOAS models vividly described the dynamic characteristics of adsorption process. Model fitting results, theoretical calculations, and comprehensive characterization revealed that adsorption is driven by electrostatic interactions between the primary amine of P-SBC/Fe3O4 film and the carboxyl group of IBP molecule, while other weak interactions are also non-ignorable. Furthermore, quantitative calculations based on density functional theory (DFT) underscored the importance of PEI functionalization. In conclusion, P-SBC/Fe3O4 film is an environmentally friendly and cost-effective adsorbent with significant potential for effectively removing IBP, while maintaining its efficacy over multiple cycles.


Assuntos
Polietilenoimina/análogos & derivados , Saccharum , Poluentes Químicos da Água , Adsorção , Celulose/química , Ibuprofeno , Saccharum/química , Polietilenoimina/química , Fenômenos Magnéticos , Cinética , Concentração de Íons de Hidrogênio
14.
J Control Release ; 368: 740-755, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38499092

RESUMO

Chronic wound treatment has emerged as a significant healthcare concern worldwide due to its substantial economic burden and the limited effectiveness of current treatments. Effective management of biofilm infections, regulation of excessive oxidative stress, and promotion of tissue regeneration are crucial for addressing chronic wounds. Hydrogel stands out as a promising candidate for chronic wound treatment. However, its clinical application is hindered by the difficulty in designing and fabricating easily and conveniently. To overcome these obstacles, we present a supermolecular G-quadruplex hydrogel with the desired multifunction via a dynamic covalent strategy and Hoogsteen-type hydrogen bonding. The G-quadruplex hydrogel is made from the self-assembly of guanosine, 2-formylphenyboronic acid, polyethylenimine, and potassium chloride, employing dynamic covalent strategy and Hoogsteen-type hydrogen bonding. In the acidic/oxidative microenvironment associated with bacterial infections, the hydrogel undergoes controlled degradation, releasing the polyethylenimine domain, which effectively eliminates bacteria. Furthermore, nanocomplexes comprising guanosine monophosphate and manganese sulfate are incorporated into the hydrogel skeleton, endowing it with the ability to scavenge reactive oxygen species and modulate macrophages. Additionally, the integration of basic fibroblast growth factor into the G-quadruplex skeleton through dynamic covalent bonds facilitates controlled tissue regeneration. In summary, the facile preparation process and the incorporation of multiple functionalities render the G-quadruplex hydrogel a highly promising candidate for advanced wound dressing. It holds great potential to transition from laboratory research to clinical practice, addressing the pressing needs of chronic wound management.


Assuntos
Surdez , Hidrogéis , Humanos , Polietilenoimina , Bandagens , Antibacterianos/farmacologia , Biofilmes
15.
Int J Pharm ; 654: 123959, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38430949

RESUMO

DNA vaccines can be a potential solution to protect global health, triggering both humoral and cellular immune responses. DNA vaccines are valuable in preventing intracellular pathogen infections, and therefore can be explored against coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). This work explored different systems based on polyethylenimine (PEI), functionalized for the first time with both cholesterol (CHOL) and mannose (MAN) to deliver parental plasmid (PP) and minicircle DNA (mcDNA) vectors encoding the receptor-binding domain (RBD) of SARS-CoV-2 to antigen-presenting cells (APCs). For comparative purposes, three different systems were evaluated: PEI, PEI-CHOL and PEI-CHOL-MAN. The systems were prepared at various nitrogen-to-phosphate group (N/P) ratios and characterized in terms of encapsulation efficiency, surface charge, size, polydispersity index (PDI), morphology, and stability over time. Moreover, in vitro transfection studies of dendritic cells (JAWS II) and human fibroblast cells were performed. Viability studies assured the biocompatibility of all nanocarriers. Confocal microscopy studies confirmed intracellular localization of systems, resulting in enhanced cellular uptake using PEI-CHOL and PEI-CHOL-MAN systems when compared with the PEI system. Regarding the RBD expression, PEI-CHOL-MAN was the system that led to the highest levels of transcripts and protein expression in JAWS II cells. Furthermore, the nanosystems significantly stimulated pro-inflammatory cytokines production and dendritic cell maturation in vitro. Overall, mannosylated systems can be considered a valuable tool in the delivery of plasmid DNA or mcDNA vaccines to APCs.


Assuntos
COVID-19 , Nanopartículas , Vacinas de DNA , Humanos , Polietilenoimina/química , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2/genética , Transfecção , DNA , Células Apresentadoras de Antígenos , Colesterol , Nanopartículas/química
16.
J Nanobiotechnology ; 22(1): 131, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532389

RESUMO

Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes. Nanostraws (NS), characterized by their hollow tubular structure, offer the advantage of flexible solution delivery compared to solid nanoneedles. However, NS struggle to stably self-penetrate the cell membrane, resulting in limited delivery efficiency. Coupling with extra physiochemical perforation strategies is a viable approach to improve their performance. This study systematically compared the efficiency of NS coupled with polyethylenimine (PEI) chemical modification, mechanical force, photothermal effect, and electric field on cell membrane perforation and DNA transfection. The results indicate that coupling NS with PEI modification, mechanical force, photothermal effects provide limited enhancement effects. In contrast, NS-electric field coupling significantly improves intracellular DNA transfection efficiency. This work demonstrates that NS serve as a versatile platform capable of integrating various physicochemical strategies, while electric field coupling stands out as a form worthy of primary consideration for efficient DNA transfection.


Assuntos
DNA , Eletroporação , Transfecção , Membrana Celular , Terapia Genética , Polietilenoimina/química
17.
J Chromatogr A ; 1720: 464802, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38507871

RESUMO

Successive multiple ionic-polymer layers (SMILs) have long since proved their worth in capillary electrophoresis as they ensure stable electroosmotic flow (EOF) and relatively high separation efficiency. Recently, we demonstrated that plotting the plate height (H) against the solute migration velocity (u) enabled a reliable quantitative evaluation of the coating performances in terms of separation efficiency. In this work, various physicochemical and chemical parameters of the SMIL coating were studied and optimized in order to decrease the slope of the ascending part of the H vs u curve, which is known to be controlled by the homogeneity in charge of the coating surface and by the possible residual solute adsorption onto the coating surface. SMILs based on poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium styrene sulfonate) (PSS) were formed and the effect of each polyelectrolyte molar mass and of the number of polyelectrolyte layers (up to 21 layers) was studied. The use of polyethylene imine as an anchoring first layer was considered. More polyelectrolyte couples based on PDADMAC, polybrene, PSS, poly(vinyl sulfate), and poly(acrylic acid) were tested. Finally, zwitterionic polymers based on the poly(α-l-lysine) scaffold were synthesized and used as the last layer of SMILs, illustrating their ability to finetune the EOF, while maintaining good separation efficiency.


Assuntos
Eletroforese Capilar , Polietilenos , Polímeros , Compostos de Amônio Quaternário , Polieletrólitos , Cátions , Eletroforese Capilar/métodos , Proteínas/análise , Polietilenoimina
18.
Photochem Photobiol Sci ; 23(4): 665-679, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38443738

RESUMO

Nanosized alginate-based particles (NAPs) were obtained in a one-pot solvent-free synthesis procedure, achieving the design of a biocompatible nanocarrier for the encapsulation of IbM6 antimicrobial peptide (IbM6). IbM6 is integrated in the nascent nanosized hydrogel self-assembly guided by electrostatic interactions and by weak interactions, typical of soft matter. The formation of the nanogel is a dynamic and complex process, which presents an interesting temporal evolution. In this work, we optimized the synthesis conditions of IbM6-NAPs based on small-angle X-ray scattering (SAXS) measurements and evaluated its time evolution over several weeks by sensing the IbM6 environment in IbM6-NAPs from photochemical experiments. Fluorescence deactivation experiments revealed that the accessibility of different quenchers to the IbM6 peptide embedded in NAPs is dependent on the aging time of the alginate network. Lifetimes measurements indicate that the deactivation paths of the excited state of the IbM6 in the nanoaggregates are reduced when compared with those exhibited by the peptide in aqueous solution, and are also dependent on the aging time of the nanosized alginate network. Finally, the entrapment of IbM6 in NAPs hinders the degradation of the peptide by trypsin, increasing its antimicrobial activity against Escherichia coli K-12 in simulated operation conditions.


Assuntos
Alginatos , Escherichia coli K12 , Polietilenoglicóis , Polietilenoimina , Nanogéis , Peptídeos Antimicrobianos , Espalhamento a Baixo Ângulo , Difração de Raios X , Peptídeos/farmacologia , Escherichia coli
19.
Bioresour Technol ; 399: 130567, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467263

RESUMO

The removal of complex pollutants from oligotrophic water is an important challenge for researchers. In this study, the HCl-modified loofah sponge crosslinked polyethyleneimine loaded with biochar (LS/PEI@biochar) biofilm reactor was adapted to achieve efficient removal of complex pollutants in oligotrophic water. On the 35 d, the average removal efficiency of chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), calcium (Ca2+), and phosphate (PO43--P) in water was 51, 95, 81, and 77 %, respectively. Additionally, it effectively used a low molecular weight carbon source. Scanning electron microscopy (SEM) results showed that the LS/PEI@biochar biocarrier had superior biofilm suspension performance. Meanwhile, analysis of the biocrystals confirmed Ca2+ and PO43- removal through the generation of CaCO3 (calcite and vaterite) and Ca5(PO4)3OH. This study demonstrated that the system has great efficiency and application prospect in treating oligotrophic water on the laboratory scale, and will be further validated for practical application on large-scale oligotrophic water.


Assuntos
Carvão Vegetal , Luffa , Poluentes Químicos da Água , Polietilenoimina , Água , Biofilmes , Carbonato de Cálcio , Nitrogênio/química , Poluentes Químicos da Água/análise
20.
ACS Appl Mater Interfaces ; 16(14): 17313-17322, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38534029

RESUMO

Glucose oxidase (Gox)-mediated starvation therapy offers a prospective advantage for malignancy treatment by interrupting the glucose supply to neoplastic cells. However, the negative charge of the Gox surface hinders its enrichment in tumor tissues. Furthermore, Gox-mediated starvation therapy infiltrates large amounts of hydrogen peroxide (H2O2) to surround normal tissues and exacerbate intracellular hypoxia. In this study, a cascade-catalyzed nanogel (A-NE) was developed to boost the antitumor effects of starvation therapy by glucose consumption and cascade reactive release of nitric oxide (NO) to relieve hypoxia. First, the surface cross-linking structure of A-NE can serve as a bioimmobilization for Gox, ensuring Gox stability while improving the encapsulation efficiency. Then, Gox-mediated starvation therapy efficiently inhibited the proliferation of tumor cells while generating large amounts of H2O2. In addition, covalent l-arginine (l-Arg) in A-NE consumed H2O2 derived from glucose decomposition to generate NO, which augmented starvation therapy on metastatic tumors by alleviating tumor hypoxia. Eventually, both in vivo and in vitro studies indicated that nanogels remarkably inhibited in situ tumor growth and hindered metastatic tumor recurrence, offering an alternative possibility for clinical intervention.


Assuntos
Neoplasias , Óxido Nítrico , Polietilenoglicóis , Polietilenoimina , Humanos , Nanogéis , Peróxido de Hidrogênio/química , Estudos Prospectivos , Neoplasias/patologia , Glucose Oxidase/química , Catálise , Glucose , Linhagem Celular Tumoral
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