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1.
J Nanosci Nanotechnol ; 21(6): 3256-3268, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34739780

RESUMO

Polyethyleneimine functionalized graphene oxide (PEI-GO) was prepared and characterized for its molecular structure and morphology. The PEI-GO is, for the first time, reported as an inhibitor against copper (Cu) corrosion in 0.5 M HCl using electrochemical studies. PEI-GO acts as a promising corrosion inhibitor for Cu with 92.24% efficiency at 100 mgL-1. The PDP studies reveal a mixed type of inhibitor behavior of PEI-GO with cathodic prevalence. Cyclic voltammetry revealed the inhibition influence of PEI-GO on the redox process of Cu corrosion. SEM and FTIR-ATR studies showed the creation of a protective layer on the Cu substrate. DFT studies revealed that the PEIGO exhibits better reactivity compared to parent PEI, and Monte Carlo simulations showed higher adsorption energy for PEI-GO on the Cu surface compared to the PEI.


Assuntos
Cobre , Polietilenoimina , Corrosão , Grafite , Ácido Clorídrico
2.
J Biomed Nanotechnol ; 17(10): 1984-1992, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706798

RESUMO

To produce an effective nanoparticle-loaded delivery system for the tumor drug erlotinib for non-small cell lung cancer (NSCLC) therapy, we loaded poly(lactic co glycolic acid) (PLGA) nanoparticles with erlotinib and used them to transport the drug to a target area. NCI-H1650 cells were cultured to test the permeability, efficiency, and anti-tumor capacity of PLGA and polyethyleneimine (PEI) drug delivery systems, and an NSCLC mouse model was prepared to further test the anti-tumor efficiency of PLGA. In tests using NCI-H1650 cells, we found that PLGA could effectively transport erlotinib into tumor cells, and release the loaded drug instantly. The infiltration efficiency was significantly higher than that of the PEI delivery system, and the same results were obtained in animal tests. PLGA-erlotinib could promote apoptosis and inhibit the migration of tumor cells more effectively than PEI-erlotinib. In the NSCLC mouse model, PLGA could more effectively reduce the tumor volume and the extent of tumor markers than the PEI delivery system. Immune function was also better rescued with the use of the PLGA system. We concluded that PLGA-erlotinib may be a good choice for lung cancer therapy in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Polietilenoimina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
3.
J Biomed Nanotechnol ; 17(9): 1726-1734, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34688317

RESUMO

The aim of this study was to test an effective nano-pole capsule loaded cis-platinum (CP) transplantation device for liver cancer (LC) therapy. A novel nano-pole capsule was designed as a new vector for storing CP. HepG2 cells and a B6/J mouse model were used to test the efficiency of polyethyleneimine-cis-platinum (PEI-CP) and poly-chitosan-cis-platinum (PC-CP). Infiltration efficiency and transplantation efficiency tests were performed to study the performance of the delivery system, and fibroblast reactions and macrophage numbers were observed, to test for immune rejection and foreign body reactions. The apoptosis rate and tumor diameter of hepatocellular carcinoma cells were used to evaluate the effect of the tumor therapy. We also studied the functional mechanism of different CP delivery systems. The infiltration and transplantation efficiencies of PC-CP were higher than that of PEI-CP; Less foreign body reaction appeared in PC system, with less fibroblast reaction and lower macrophage reaction. The clinical efficacy of PC-CP in terms of tumor apoptosis and diameter reduction was superior to that of PEI-CP. We demonstrated that PC-CP had a more significant alteration effect on mTOR, P-Ak, LC3 and P53. The PC system can better deliver and release drugs than PEI-CP, and may be a better choice for LC therapy in the future.


Assuntos
Quitosana , Neoplasias Hepáticas , Nanopartículas , Preparações Farmacêuticas , Animais , Cisplatino , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Polietilenoimina , Transfecção
4.
Biomater Sci ; 9(19): 6623-6640, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582532

RESUMO

Biocompatible hydrophilic polyethylene glycol (PEG) is widely used in biomedical applications, such as drug or gene delivery, tissue engineering or as an antifouling component in biomedical devices. Experimental studies have shown that the size of PEG can weaken polycation-polyanion interactions, like those between branched polyethyleneimine (b-PEI) and DNA in gene carriers, but details of its cause and underlying interactions on the atomic scale are still not clear. To better understand the interaction mechanisms in the formation of polyplexes between b-PEI-PEG based carriers and DNA, we have used a combination of in silico tools and experiments on three multicomponent systems differing in PEG MW. Using the PEI-PEG-squalene-dsDNA systems of the same size, both in the all-atom MD simulations and in experimental in-gel electrophoresis measurements, we found that the binding between DNA and the vectors is highly influenced by the size of PEG, with the binding efficiency increasing with a shorter PEG length. The mechanism of how PEG interferes with the binding between PEI and DNA is explained using a two-step MD simulation protocol that showed that the DNA-vector interactions are influenced by the PEG length due to the hydrogen bond formation between PEI and PEG. Although computationally demanding we find it important to study molecular systems of the same size both in silico and in a laboratory and to simulate the behaviour of the carrier prior to the addition of bioactive molecules to understand the molecular mechanisms involved in the formation of the polyplex.


Assuntos
Polietilenoglicóis , Esqualeno , Simulação por Computador , DNA , Tamanho da Partícula , Polietilenoimina , Transfecção
5.
Anal Chem ; 93(38): 12854-12861, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34516097

RESUMO

Fluorescence titration using magnetic nanoparticles (FTMN) was performed as a rapid, inexpensive, and simple method for quantifying the amount of fluorophore-intercalated plasmid DNA on these DNA attractive nanoparticles. Binding of the propidium iodide (PI)-intercalated DNA (PI/DNA) to polyethylenimine (PEI)-coated monodisperse iron oxide magnetic nanoparticles (PEI-MNs) was confirmed with transmission electron microscopy after the two species were mixed in water for less than a minute. The amount of DNA on PEI-MNs in aqueous solution, however, could not be easily determined using direct fluorescence measurements due to strong scattering by aggregated MNs, especially at high nanoparticle concentrations. Instead, fluorescence measurements were taken immediately after the solution of PI/DNA and PEI-MN mixtures was treated with a magnet to pull the PEI-MNs out of the solution. The detected fluorescence signal of the remaining free PI/DNA in the solution decreased as the concentration of PEI-MNs in the pre-treated solutions increased, resulting in a titration curve, which was used to determine the amount of DNA on MNs, the dissociation constant, and binding energy after the concentration of PEI-MNs was calibrated with microwave-plasma atomic emission spectroscopy. Quantitative polymerase chain reaction was used to understand the binding of DNA to MNs and to measure the amount of free PI/DNA in solution, and the results were similar to those obtained with the FTMN method.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , DNA , Magnetismo , Plasmídeos/genética , Polietilenoimina
6.
ACS Nano ; 15(10): 15874-15891, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34586802

RESUMO

The clinical application of small interfering RNA (siRNA) drugs provides promising opportunities to develop treatment strategies for autoimmune inflammatory diseases. In this study, siRNAs targeting the endoplasmic reticulum to nucleus signaling 1 (ERN1) gene (siERN1) were screened. Two cationic polymers, polyethylenimine (PEI) and poly(ß-amino amine) (PBAA), which can improve the efficiency of the siRNA transfection, were used as siERN1 delivery carriers. They were implemented to construct a nanodrug delivery system with macrophage-targeting ability and dual responsiveness for the treatment of autoimmune inflammatory diseases. In terms of the mechanism, siERN1 can regulate the intracellular calcium ion concentration by interfering with the function of inositol 1,4,5-trisphosphate receptor 1/3 (IP3R1/3) and thus inducing M2 polarization of macrophages. Furthermore, siERN1-nanoprodrug [FA (folic acid)-PEG-R(RKKRRQRRR)-NPs(ss-PBAA-PEI)@siERN1] acts as a conductor of macrophage polarization by controlling the calcium ion concentration and is an inhibitor of MyD88-dependent Toll-like receptor signaling. The results revealed that the FA-PEG-R-NPs@siERN1 has universal biocompatibility, long-term drug release responsiveness, superior targeting properties, and therapeutic effects in mouse collagen-induced arthritis and inflammatory bowel disease models. In conclusion, this study reveals a potential strategy to treat autoimmune inflammatory disorders.


Assuntos
Polietilenoimina , Receptores Toll-Like , Animais , Macrófagos , Camundongos , RNA Interferente Pequeno , Transfecção
7.
ACS Nano ; 15(10): 15920-15929, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34591443

RESUMO

Coating living cells with a functional shell has been regarded as an effective way to protect them against environmental stress, regulate their biological behaviors, or extend their functionalities. Here, we reported a facile method to prepare fully or partially coated shells on an individual yeast cell surface by visible light-induced graft polymerization. In this strategy, yeast cells that were surface-absorbed with polyethylenimine (PEI) were deposited on the negatively charged glass slide to form a single layer by electrostatic interaction. Then, surface-initiated graft polymerization of poly(ethylene glycol) diacrylate (PEGDA) on yeast cells under visible light irradiation was carried out to generate cross-linked shells on the cells. The process of surface modification had negligible influence on the viability of yeast cells due to the mild reaction condition. Additionally, compared to the native yeast cells, a 17.5 h of delay in division was observed when the graft polymerization was performed under 15 mW/cm2 irradiation for 30 min. Introducing artificial shell endowed yeast cells with significant resistance against lyticase, and the protection can be enhanced by increasing the thickness of shell. Moreover, the partially coated yeast cells would be prepared by simply adjusting the reaction condition such as irradiation density and time. By immobilizing urease on the functional patch, the asymmetrically modified yeast cells exhibited self-propelling capability, and the speed of directional movement reached 4 µm/s in the presence of 200 mM urea. This tunable coating individual cell strategy with varying functionality has great potential applications in fields of cell-based drug delivery, cell therapy, biocatalysis, and tissue engineering.


Assuntos
Luz , Polietilenoimina , Sistemas de Liberação de Medicamentos , Polimerização , Eletricidade Estática
8.
ACS Biomater Sci Eng ; 7(10): 4933-4945, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34583510

RESUMO

Titanium and its alloys have been widely used as bone implants, but for reduced treatment span, improvements are urgently needed to achieve faster and better osteointegration. In this study, we found that miR-132-3p inhibited bone-marrow-derived stem cell (BMSC) osteogenic differentiation via targeting BMP2, and that inhibiting miR-132-3p could significantly improve the osteogenic capability of BMSCs. Moreover, we fabricated a biocompatible selenomethionine (SEMET)-modified polyethylene glycol (PEG)/polyethylenimine (PEI) nanoparticle (SeNP) cross-linked with 0.2% gelatin solutions and delivered miR-132-3p inhibitor to biofunctionalize alkali heat-treated titanium implants, resulting in the development of a novel coating for reverse transfection. The biological performances of PEG/PEI/miR-132-3p inhibitor and SeNP/miR-132-3p inhibitor-biofunctionalized titanium were compared. The biological effects, including cell viability, cytotoxicity, adhesion, cellular uptake, and osteogenic capacity of SeNP/miR-132-3p inhibitor-biofunctionalized titanium implants, were then assessed. Results showed that SeNPs presented appropriate morphology, diameter, and positive zeta potential for efficient gene delivery. The transfection efficiency of the SeNP/miR-132-3p inhibitor was comparable to that of the PEG/PEI/miR-132-3p inhibitor, but the former induced less reactive oxygen species (ROS) production and lower apoptosis rates. Confocal laser scanning microscopy (CLSM) demonstrated that SeNP/miR-132-3p inhibitor nanoparticles released from the titanium surfaces and were taken up by adherent BMSCs. In addition, the release profile showed that transfection could obtain a long-lasting silencing effect for more than 2 weeks. The cell viability, cytotoxicity, and cell spreading of SeNP/miRNA-132-3p inhibitor-biofunctionalized titanium were comparable with those of untreated titanium and the SeNP/miRNA-132-3p inhibitor negative control (NC)-biofunctionalized titanium but resulted in higher ALP activity and osteogenic gene expression levels. In vivo animal studies further certified that SeNP/miRNA-132-3p inhibitor nanoparticles from titanium surfaces promoted osteointegration, which was revealed by microcomputed tomography (micro-CT) and histological observations. Taken together, these findings suggested that selenomethionine-modified PEI-based nanoparticles could achieve better biocompatibility. Moreover, titanium implants biofunctionalized by SeNP/miRNA-132-3p inhibitor nanoparticles might have significant clinical potential for more effective osteointegration.


Assuntos
MicroRNAs , Nanopartículas , Animais , MicroRNAs/genética , Osteogênese , Polietilenoimina , Selenometionina , Titânio , Microtomografia por Raio-X
9.
J Control Release ; 338: 537-547, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34481924

RESUMO

mRNA-based therapy has been evaluated in preclinical and clinical studies for the treatment of a wide variety of disease such as cancer immunotherapies and infectious disease vaccines. However, it remains challenging to development safe and efficient delivery system. Here, we have designed a novel self-assembled polymeric micelle based on vitamin E succinate modified polyethyleneimine copolymer (PVES) to delivery mRNA. In vitro, PVES could transfect mRNA into multiple cell lines such as HEK-293T, HeLa and Vero and the transfection efficiencies were much higher than PEI 25 k. In addition, the cytotoxicity of PVES was much lower than PEI 25 k. Furthermore, mice administered intramuscularly with PVES/SARS-CoV-2 mRNA vaccine induced potent antibody response and show no obvious toxicity. These results demonstrated the potential of PVES as a safe and effective delivery carrier for mRNA.


Assuntos
COVID-19 , Micelas , Animais , Vacinas contra COVID-19 , Células HeLa , Humanos , Camundongos , Polietilenoimina , RNA Mensageiro , SARS-CoV-2 , Transfecção
10.
Anal Chem ; 93(36): 12237-12242, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34474555

RESUMO

Herein, we developed a novel method for the efficient capture of waterborne bacteria by creating an autonomous internal reflux of the magnetic nanoparticle chains (MNCs) inside a flow channel. A glass tube containing positively charged polyethyleneimine-coated MNCs (PEI-MNCs) was placed at the center of a Halbach ring, generating a strong and uniform magnetic field inside the ring. When a bacteria-spiked solution was injected into the tube, the target bacteria bound to the PEI-MNCs via an electrostatic interaction remained in the tube, whereas the unbound bacteria left the tube. Some PEI-MNC-bacteria complexes left the glass tube at high flow rates because of the drag force, which reduced the capture efficiency of the device. The loss of the PEI-MNC-bacteria complexes at high flow rates was suppressed by placing a k0 ring behind the Halbach ring. The k0 ring was used to apply a magnetic force in the opposite direction of the solution flow and create an autonomous reflux of the PEI-MNCs inside the glass tube, reducing their loss and increasing their capture efficiency. The capture efficiency of Escherichia coli O157 was determined based on the cell count to be greater than 90% at a flow rate of 15 mL/min. E. coli O157 was detected using quantitative polymerase chain reaction, and the limits of detection were 2 and 3 cfu/mL in deionized water and river water, respectively.


Assuntos
Escherichia coli O157 , Nanopartículas de Magnetita , Bactérias , Magnetismo , Polietilenoimina
11.
Langmuir ; 37(37): 10902-10913, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477388

RESUMO

We here demonstrate the utilization of reactive layer-by-layer (rLBL) assembly to form a nanogel coating made of branched polyethylenimine (BPEI) and alkyne containing polyester (PE) on a gold surface. The rLBL is generated by the rapid aza-Michael addition reaction of the alkyne group of PE and the -NH2 groups of BPEI by yielding a homogeneous gel coating on the gold substrate. The thickness profile of the nanogel revealed that a 400 nm thick coating is formed by six multilayers of rLBL, and it exhibits 50 nm roughness over 8 µm distance. The LBL characteristics were determined via depth profiling analysis by X-ray photoelectron spectroscopy, and it has been shown that a 70-100 nm periodic increase in gel thickness is a consequence of consecutive cycles of rLBL. A detailed XPS analysis was performed to determine the yield of the rLBL reaction: the average yield was deduced as 86.4% by the ratio of the binding energies at 286.26 eV, (C═CN-C bond) and 283.33 eV, (C≡C triple bond). The electrochemical characterization of the nanogels ascertains that up to the six-multilayered rLBL of BPEI-PE is electroactive, and the nanogel permeability had led to drive mass and charge transfer effectively. These results promise that nanogel formation by rLBL films may be a straightforward modification of electrodes approach, and it exhibits potential for the application of soft biointerfaces.


Assuntos
Poliésteres , Polietilenoimina , Nanogéis , Polietilenoglicóis
12.
Mater Sci Eng C Mater Biol Appl ; 128: 112323, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474874

RESUMO

The standard scaffold-mediated delivery of drugs/biomolecules has been successful due to the unique attributes of scaffolds, specifically the electrospun polymeric scaffolds that mimic ECM are well suited for advanced regenerative applications. Cardiac tissue engineering includes the interpretation of cellular and molecular mechanisms concerning heart regeneration and identifying an efficient reprogramming strategy to overcome the limitation of delivery systems and enhance the reprogramming efficiency. This study is a step towards developing a functional scaffold through a parallel interpretation of electrospun PLLA scaffolds with two distinct topologies to achieve sustained delivery of two muscle-specific microRNAs (miR-1 and miR-133a) to directly reprogram the adult human cardiac fibroblasts into cardiomyocyte-like cells. Polyethyleneimine was used to form stable PEI-miRNA complexes through electrostatic interactions. These complexes were immobilized on the electrospun smooth and porous scaffolds, where a loading efficiency of ~96% for the fibronectin modified and ~38% for unmodified surfaces was observed, regardless of their surface topology. The in-vitro release experiment exhibited a biphasic release pattern of PEI-miRNA polyplexes from the scaffolds. These dual miRNA scaffold systems proved to be an excellent formulation since their combinatorial effect involving the topographic cues of electrospun fibers, and dual miRNAs helped control the cardiac fibroblast cell fate precisely.


Assuntos
MicroRNAs , Fibroblastos , Humanos , MicroRNAs/genética , Miócitos Cardíacos , Polietilenoimina , Engenharia Tecidual , Tecidos Suporte
13.
Mater Sci Eng C Mater Biol Appl ; 128: 112358, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474905

RESUMO

Bioreducible polyethylenimines (SSPEIs) are promising non-viral carriers for cancer gene therapy. However, the availability of significant gene transfection activity by SSPEIs remains a challenge. Herein, an essential step was taken to ascertain whether or not the disulfide bonds of SSPEIs play a critical role in promoting significant gene transfection activity in different tissues. Initially, a disulfide-linked linear polyethylenimine (denoted as SSLPEI) consisting of one 5.0 kDa LPEI main chain and three disulfide-linked 5.7 kDa LPEI grafts was designed and prepared to possess similar molecular weight with commercialized 25 kDa LPEI as a positive control. The SSLPEI could induce superior in vitro transfection activity in different cells to the LPEI control as well as low cytotoxicity. Notably, such enhanced in vitro transfection effect by the SSLPEI was more marked in type-II alveolar epithelial cells compared to different cancer cells. In a Balb/c nude mouse model bearing SKOV-3 tumor, the SSLPEI caused parallel level of transgene expression with the LPEI control in the tumor but significantly higher level in the mouse lung. Furthermore, the SSLPEI and LPEI groups afforded an identical antitumor efficacy against the SKOV-3 tumor via intravenous delivery of a shRNA for silencing VEGF expression in the tumor. However, via intravenous delivery of an interleukin-12 (IL-12) gene into metastatic lung cancers in a C57BL/6 mouse model, the SSLPEI group exerted markedly higher IL-12 expression level in the mouse lung and peripheral blood as compared to the LPEI group, thereby boosting IL-12 immunotherapy against the lung metastasis with longer medium survival time. The results of this work elicit that the disulfide bonds of SSPEIs play a pivotal role in enhancing gene transfection activity selectively in the lung tissue rather than solid tumor, enabling high translational potential of SSPEIs for non-viral gene therapy against metastatic lung cancers.


Assuntos
Neoplasias Pulmonares , Polietilenoimina , Animais , Dissulfetos , Terapia Genética , Interleucina-12/genética , Pulmão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Camundongos , Camundongos Endogâmicos C57BL , Transfecção
14.
Molecules ; 26(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34577079

RESUMO

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.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polietilenoglicóis/farmacologia , Polietilenoimina/farmacologia , Pele/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Biofilmes/efeitos dos fármacos , Sinais (Psicologia) , Fatores de Transcrição Forkhead/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Nanogéis/química , Nanogéis/uso terapêutico , PPAR gama/metabolismo , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Polietilenoimina/química , Polietilenoimina/uso terapêutico , Ratos , Pele/metabolismo , Syzygium/química , Thymus (Planta)/química , Receptor 2 Toll-Like/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Wnt/metabolismo
15.
Int J Nanomedicine ; 16: 5167-5183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354350

RESUMO

Introduction: Smart theranostic nanosystems own a favorable potential to improve internalization within tumor while avoiding nonspecific interaction with normal tissues. However, development of this type of theranostic nanosystems is still a challenge. Methods: In this study, we developed the iodine-131 (131I)-labeled multifunctional polyethylenimine (PEI)/doxorubicin (DOX) complexes with pH-controlled cellular uptake property for enhanced single-photon emission computed tomography (SPECT) imaging and chemo/radiotherapy of tumors. Alkoxyphenyl acylsulfonamide (APAS), a typical functional group that could achieve improved cellular uptake of its modified nanoparticles, was utilized to conjugate onto the functional PEI pre-modified with polyethylene glycol (PEG) with terminal groups of monomethyl ether and N-hydroxysuccinimide (mPEG-NHS), PEG with terminal groups of maleimide and succinimidyl valerate (MAL-PEG-SVA) through sulfydryl of APAS and MAL moiety of MAL-PEG-SVA. This was followed by conjugation with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), acetylating leftover amines of PEI, complexing DOX and labeling 131I to generate the theranostic nanosystems. Results: The synthesized theranostic nanosystems exhibit favorable water solubility and stability. Every functional PEI can complex approximately 12.4 DOX, which could sustainably release of DOX following a pH-dependent manner. Remarkably, due to the surface modification of APAS, the constructed theranostic nanosystems own the capacity to achieve pH-responsive charge conversion and further lead to improved cellular uptake in cancer cells under slightly acidic condition. Above all, based on the coexistence of DOX and radioactive 131I in the single nanosystem, the synthesized nanohybrid system could afford enhanced SPECT imaging and chemo/radioactive combination therapy of cancer cells in vitro and xenografted tumor model in vivo. Discussion: The developed smart nanohybrid system provides a novel strategy to improve the tumor theranostic efficiency and may be applied for different types of cancer.


Assuntos
Neoplasias , Tomografia Computadorizada de Emissão de Fóton Único , Linhagem Celular Tumoral , Quimiorradioterapia , Doxorrubicina , Humanos , Concentração de Íons de Hidrogênio , Radioisótopos do Iodo , Neoplasias/terapia , Polietilenoglicóis , Polietilenoimina
16.
Water Environ Res ; 93(11): 2780-2794, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34453770

RESUMO

This study concerns the preparation of novel adsorbent prepared from calcium alginate bead modified with polyethyleneimine (PEI-CaAlg). The adsorption capacity of the PEI-CaAlg was examined by Remazol Brilliant Blue R (RBBR) and phosphate adsorption. PEI-CaAlg showed high removal efficiencies for RBBR (90.48%) and phosphate (88.10%). The removal of both RBBR and phosphate onto the PEI-CaAlg followed the Freundlich isotherm and the second-order model. The adsorption was studied in terms of thermodynamic and found to be feasible and spontaneous in nature. The reusability of the modified alginate beads was also examined up to five cycles. The removal efficiency was 90.48% at the first cycle and decreased to 75.15% at the end of the fourth cycle. The adsorption of color and phosphate from real textile wastewater was also instigated. The removal efficiencies for color and phosphate ions reached 80.24% and 90.00%, respectively. Therefore, the prepared PEI-CaAlg can be considered as a novel, eco-friendly, and cost-effective adsorbent for simultaneous dye and phosphate adsorption. PRACTITIONER POINTS: This study aims to modify the surface of calcium alginate beads with polyethyleneimine (PEI). The adsorption of RBBR and phosphate by the modified alginate beads (PEI-CaAlg) was investigated. PEI is an organic polymer with a linear/branch shape, which can increase the active sites on the adsorbent surface. PEI has one nitrogen atom in every three atoms provides a positive charge that can complex with the negatively charged molecules. The adsorption of RBBR and phosphate were carried out onto PEI-CaAlg.


Assuntos
Alginatos , Poluentes Químicos da Água , Adsorção , Antraquinonas , Concentração de Íons de Hidrogênio , Cinética , Fosfatos , Polietilenoimina
17.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445774

RESUMO

Polyethyleneimine (PEI) induced immune responses were investigated in human bronchial epithelial (hBE) cells and mice. PEI rapidly induced ATP release from hBE cells and pretreatment with glutathione (GSH) blocked the response. PEI activated two conductive pathways, VDAC-1 and pannexin 1, which completely accounted for ATP efflux across the plasma membrane. Moreover, PEI increased intracellular Ca2+ concentration ([Ca2+]i), which was reduced by the pannexin 1 inhibitor, 10Panx (50 µM), the VDAC-1 inhibitor, DIDS (100 µM), and was nearly abolished by pretreatment with GSH (5 mM). The increase in [Ca2+]i involved Ca2+ uptake through two pathways, one blocked by oxidized ATP (oATP, 300 µM) and another that was blocked by the TRPV-1 antagonist A784168 (100 nM). PEI stimulation also increased IL-33 mRNA expression and protein secretion. In vivo experiments showed that acute (4.5 h) PEI exposure stimulated secretion of Th2 cytokines (IL-5 and IL-13) into bronchoalveolar lavage (BAL) fluid. Conjugation of PEI with ovalbumin also induced eosinophil recruitment and secretion of IL-5 and IL-13 into BAL fluid, which was inhibited in IL-33 receptor (ST2) deficient mice. In conclusion, PEI-induced oxidative stress stimulated type 2 immune responses by activating ATP-dependent Ca2+ uptake leading to IL-33 secretion, similar to allergens derived from Alternaria.


Assuntos
Trifosfato de Adenosina/imunologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Imunidade/efeitos dos fármacos , Nanopartículas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Polietilenoimina/farmacologia , Alérgenos/imunologia , Animais , Cálcio/imunologia , Células Cultivadas , Citocinas/imunologia , Feminino , Humanos , Imunidade/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/imunologia , RNA Mensageiro/imunologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia
18.
Food Res Int ; 147: 110564, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34399540

RESUMO

Nanogel carriers are rapidly emerged as a major delivery strategy in the fields of food, biology and medicine for small particle size, excellent solubility, high loading, and controlled release. Natural polysaccharides and proteins are selected for the preparation of biocompatible, biodegradable, low toxic, and less immunogenic nanogels. Different polysaccharides and proteins form complex nanogels through different interaction forces (e.g., electrostatic interaction and hydrophobic interaction). The present review pursues three aims: 1) to introduce several well-known dietary polysaccharides (chitosan, dextran and alginate) and proteins (whey protein and lysozyme); 2) to discuss the types, preparation methods, chemical interactions and properties of various biocompatible complex carriers; 3) to present the application and prospect of polysaccharide-protein complex in bioactive ingredient delivery, nutrient encapsulation and flavor protection. We expect that the integration with nano-intelligent technology will improve the functional ingredient loading, recognition specificity and controlled release capabilities of polysaccharide-protein nanocomposites to generate new intelligent nanogels in the field of food industry in the future.


Assuntos
Portadores de Fármacos , Polietilenoimina , Nanogéis , Polietilenoglicóis , Polissacarídeos
19.
Anal Chem ; 93(33): 11451-11460, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34425678

RESUMO

The sensitive and selective determination of peroxide-based explosives (PBEs) in the field/on site is an important analytical challenge. Most methods claiming to detect PBEs are indirect, actually detecting their decomposition product, H2O2. Here, we present an electrochemical sensor for direct detection of organic peroxide explosives, that is, triacetone triperoxide (TATP) and hexamethylenetriperoxide diamine (HMTD), using well-dispersed multiwalled carbon nanotubes/polyethyleneimine (MWCNTs/PEI)-modified glassy carbon (GC) electrode, namely, GC/MWCNTs/PEI electrode. This is the first use of the conductive polyelectrolyte PEI as an electrode modifier for pristine PBE sensing. The potential range, scan rate, solvent selection, and supporting electrolyte concentration were optimized for PBEs. As a distinct advantage over other similar methods, our sensor electrode responded to intact TATP solutions in neutral medium, meaning that TATP did not interact with acids/bases that would transform it into H2O2. Calibration curves were linear in the range of 10-200 mg L-1 for TATP and 25-200 mg L-1 for HMTD. Using differential pulse voltammetry, detection limits of 1.5 mg L-1 TATP and 3.0 mg L-1 HMTD were obtained from direct electrochemical reduction in 80/20% (v/v) H2O-acetone solvent medium. Electroactive camouflage materials such as passenger belongings (e.g., sweetener, detergent, sugar, and paracetamol-caffeine-based analgesic drugs), common ions, and other explosives were shown not to interfere with the proposed method. The nonresponsive behavior of our electrode to H2O2 prevents "false positives" from other peroxide materials of everyday use. This electrochemical sensor could also detect other nitro-explosives at different potentials and was statistically validated against standard GC-MS and spectrophotometric methods.


Assuntos
Substâncias Explosivas , Nanotubos de Carbono , Técnicas Eletroquímicas , Eletrodos , Peróxido de Hidrogênio , Peróxidos , Polietilenoimina
20.
Molecules ; 26(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34443415

RESUMO

MiR-34a, an important tumor suppressor, has been demonstrated to possess great potential in tumor gene therapy. To achieve the upregulation of miR-34a expression level, an oligoethyleneimine (OEI) derivative was constructed and employed as the carrier through the modification with lipoic acid (LA), namely LA-OEI. In contrast to OEI, the derivative LA-OEI exhibited superior transfection efficiency measured by confocal laser scanning microscopy and flow cytometry, owing to rapid cargo release in the disulfide bond-based reduction sensitive pattern. The anti-proliferation and anti-migration effects were tested after the miR-34a transfection to evaluate the anti-tumor response, using human cervical carcinoma cell line HeLa as a model. The delivery of LA-OEI/miR-34a nanoparticles could achieve obvious anti-proliferative effect caused by the induction of cell apoptosis and cell cycle arrest at G1 phase. In addition, it could inhibit the migration of tumor cells via the downregulation of MMP-9 and Notch-1 level. Overall, the LA-OEI-mediated miR-34a delivery was potential to be used as an effective way in the tumor gene therapy.


Assuntos
Antineoplásicos/farmacologia , MicroRNAs/metabolismo , Polietilenoimina/química , Ácido Tióctico/química , Transfecção , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células HeLa , Humanos , MicroRNAs/genética , Nanopartículas/ultraestrutura , Polietilenoimina/síntese química , Ácido Tióctico/síntese química , Cicatrização/efeitos dos fármacos
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