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1.
Int J Nanomedicine ; 15: 5131-5146, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764941

RESUMO

Background: Gene therapy is considered a novel way to treat osteosarcoma, and microRNAs are potential therapeutic targets for osteosarcoma. miR-214 has been found to promote osteosarcoma aggression and metastasis. Graphene oxide (GO) is widely used for gene delivery for the distinct physiochemical properties and minimal cytotoxicity. Methods: Polyethyleneimine (PEI)-functionalized GO complex was well-prepared and loaded with miR-214 inhibitor at different concentrations. The load efficacy was tested by gel retardation assay and the cy3-labeled fluorescence of cellular uptake. The experiments of wound healing, immunofluorescence staining, Western blot, qRT-PCR and immunohistochemical staining were performed to measure the inhibitory effect of the miR-214 inhibitor systematically released from the complexes against MG63, U2OS cells and xenograft tumors. Results: The systematic mechanistic elucidation of the efficient delivery of the miR-214 inhibitor by GO-PEI indicated that the inhibition of cellular miR-214 caused a decrease in osteosarcoma cell invasion and migration and an increase in apoptosis by targeting phosphatase and tensin homolog (PTEN). The synergistic combination of the GO-PEI-miR-214 inhibitor and CDDP chemotherapy showed significant cell death. In a xenograft mouse model, the GO-PEI-miR-214 inhibitor significantly inhibited tumor volume growth. Conclusion: This study indicates the potential of functionalized GO-PEI as a vehicle for miRNA inhibitor delivery to treat osteosarcoma with low toxicity and miR-214 can be a good target for osteosarcoma therapy.


Assuntos
Grafite/química , MicroRNAs/antagonistas & inibidores , Terapia de Alvo Molecular , Osteossarcoma/tratamento farmacológico , PTEN Fosfo-Hidrolase/metabolismo , Polietilenoimina/química , Polietilenoimina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Ósseas/patologia , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/genética , Terapia Combinada , Humanos , Camundongos , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia
2.
Int J Nanomedicine ; 15: 4237-4256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606675

RESUMO

With the passage of time and more advanced societies, there is a greater emergence and incidence of disease and necessity for improved treatments. In this respect, nowadays, aptamers, with their better efficiency at diagnosing and treating diseases than antibodies, are at the center of attention. Here, in this review, we first investigate aptamer function in various fields (such as the detection and remedy of pathogens, modification of nanoparticles, antibiotic delivery and gene delivery). Then, we present aptamer-conjugated nanocomplexes as the main and efficient factor in gene delivery. Finally, we focus on the targeted co-delivery of genes and drugs by nanocomplexes, as a new exciting approach for cancer treatment in the decades ahead to meet our growing societal needs.


Assuntos
Antibacterianos/farmacologia , Aptâmeros de Nucleotídeos/química , Técnicas de Transferência de Genes , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas/ultraestrutura , Polietilenoimina/química
3.
Int J Nanomedicine ; 15: 4483-4500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606690

RESUMO

Purpose: Tumor metastasis and drug resistance have always been vital aspects to cancer mortality and prognosis. To compromise metastasis and drug resistance, a nanoparticle IPPD-PHF2 (IR780/PLGA-PEI(Dox)-PHF2) has been engineered to accomplish efficient targeted epigenotherapy forced by PHF2-induced MET (mesenchymal to epithelial transition). Materials and Methods: IPPD-PHF2 nanoparticle was synthesized and characterized by several analytical techniques. The transfection efficiency of IPP-PHF2 (IR780/PLGA-PEI-PHF2) was compared with PP-PHF2 (PLGA-PEI-PHF2) in vitro by WB and in vivo by IHC, and the cytotoxicity of IPP was compared with Lipo2000 in vitro by CCK8 assay. The inhibition of cancer cell migration caused by PHF2-upregulation was tested by wound healing assay, and the enhanced chemotherapeutic sensitivity was detected by flow cytometry. Tumor-targeting property of IPPD-PHF2 was proved by fluorescent imaging in vivo with MDA-MB-231 tumor-bearing nude mice. Except for fluorescent imaging ability, considerable photoacoustic signals of IPPD-PHF2 at tumor sites were verified. The anti-tumor activity of IPPD-PHF2 was investigated using in vivo human breast cancer MDA-MB-231 cell models. Results: Tumor-targeting nanoparticle IPPD-PHF2 had an average size of about 319.2 nm, a stable zeta potential at about 38 mV. The encapsulation efficiency of doxorubicin was around 39.28%, and the adsorption capacity of plasmids was about 64.804 µg/mg. Significant up-regulation of PHF2 induced MET and caused reduced migration as well as enhanced chemotherapeutic sensitivity. Either IPPD (IR780/PLGA-PEI(Dox)) or IPP-PHF2 (IR780/PLGA-PEI-PHF2) presented minor therapeutic effects, whereas IPPD-PHF2 specifically accumulated within tumors, showed extraordinary transfection efficiency specifically in tumor sites, acted as inhibitors of metastasis and proliferation, and presented good multimodality imaging potentials in vivo. Conclusion: IPPD-PHF2 NPs is a promising tool to bring epigenotherapy into a more practical era, and the potential application of harm-free multimodality imaging guidance is of great value.


Assuntos
Antineoplásicos/uso terapêutico , Epigênese Genética , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Transfecção , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Indóis/química , Camundongos Nus , Nanopartículas/ultraestrutura , Metástase Neoplásica , Técnicas Fotoacústicas , Polietilenoimina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química
4.
Nat Protoc ; 15(8): 2728-2757, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32669637

RESUMO

Although organic nanomaterials and inorganic nanoparticles possess inherent flexibility, facilitating functional modification, increased intracellular uptake and controllable drug release, their underlying cytotoxicity and lack of specificity still cause safety concerns. Owing to their merits, which include natural biocompatibility, structural stability, unsurpassed programmability, ease of internalization and editable functionality, tetrahedral DNA nanostructures show promising potential as an alternative vehicle for drug delivery and biomedical treatment. Here, we describe the design, fabrication, purification, characterization and potential biomedical applications of a self-assembling tetrahedral DNA nanostructure (TDN)-based multifunctional delivery system. First, relying on Watson-Crick base pairing, four single DNA strands form a simple and typical pyramid structure via one hybridization step. Then, the protocol details four different modification approaches, including replacing a short sequence of a single DNA strand by an antisense peptide nucleic acid, appending an aptamer to the vertex, direct incubation with small-molecular-weight drugs such as paclitaxel and wogonin and coating with protective agents such as cationic polymers. These modified TDN-based complexes promote the intracellular uptake and biostability of the delivered molecules, and show promise in the fields of targeted therapy, antibacterial and anticancer treatment and tissue regeneration. The entire duration of assembly and characterization depends on the cargo type and modification method, which takes from 2 h to 3 d.


Assuntos
DNA/química , Portadores de Fármacos/química , Desenho de Fármacos , Nanoestruturas/química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , DNA/farmacologia , Regeneração Tecidual Guiada , Humanos , Células MCF-7 , Peso Molecular , Polietilenoimina/química
5.
J Vis Exp ; (160)2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32658190

RESUMO

Due to drug resistance and toxicity in healthy cells, use of doxorubicin (DOX) has been limited in clinical cancer therapy. This protocol describes the designing of poly(ethylenimine) grafted with polyethylene glycol (PEI-g-PEG) copolymer functionalized gold nanoparticles (AuNPs) with loaded aptamer (AS1411) and DOX through amide reactions. AS1411 is specifically bonded with targeted nucleolin receptors on cancer cells so that DOX targets cancer cells instead of healthy cells. First, PEG is carboxylated, then grafted to branched PEI to obtain a PEI-g-PEG copolymer, which is confirmed by 1H NMR analysis. Next, PEI-g-PEG copolymer coated gold nanoparticles (PEI-g-PEG@AuNPs) are synthesized, and DOX and AS1411 are covalently bonded to AuNPs gradually via amide reactions. The diameter of the prepared AS1411-g-DOX-g-PEI-g-PEG@AuNPs is ~39.9 nm, with a zeta potential of -29.3 mV, indicating that the nanoparticles are stable in water and cell medium. Cell cytotoxicity assays show that the newly designed DOX loaded AuNPs are able to kill cancer cells (A549). This synthesis demonstrates the delicate arrangement of PEI-g-PEG copolymers, aptamers, and DOX on AuNPs that are achieved by sequential amide reactions. Such aptamer-PEI-g-PEG functionalized AuNPs provide a promising platform for targeted drug delivery in cancer therapy.


Assuntos
Aptâmeros de Nucleotídeos/química , Doxorrubicina/química , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Ouro/química , Nanopartículas Metálicas/química , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , Células A549 , Técnicas de Química Sintética , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Humanos , Oligodesoxirribonucleotídeos/química , Polietilenoimina/química
6.
Chemosphere ; 258: 127316, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32559494

RESUMO

In this study, graphene oxide (GO), polyethyleneimine (PEI) and potassium hydroxide (KOH) were used to synthesize reduced graphene oxide (rGO/PEI-KOH) nanocomposite. The presence and grafting of PEI molecules on the reduced GO surface were assessed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) analyses. The rGO/PEI-KOH nanocomposite was successfully applied for hexavalent chromium, Cr(VI), wastewater elimination. The resulting rGO/PEI-KOH adsorbent was found to be highly effective for Cr(VI) removal at low pH values and achieved a maximum capacity of experimental adsorption of 398.9 mg/g, which is one of the highest sorption capacity of most GO- and PEI-based adsorbents reported in the literature up to date. Studying the adsorption mechanism, the sorption isotherm revealed that the modified-Langmuir model was the best fit and Cr(VI) removal follows a pseudo-second-order kinetics, with the predominance of intraparticle diffusion during the first step of adsorption. XPS analysis indicated the presence of appreciable amount of Cr(III) on the adsorbent surface, which suggests that the adsorbed Cr(VI) ions were effectively reduced to Cr(III) on the rGO/PEI-KOH adsorbent surface (∼70% of the total adsorbed Cr). Cr(VI) adsorption and subsequent reduction to Cr(III) both contributed to the Cr(VI) removal. The results of the present study highlight the benefits of rGO/PEI-KOH like low cost, environmentally friendly, large toxic Cr(VI) ions adsorption capacity and its effective reduction to less-toxic Cr(III).


Assuntos
Cromo/química , Grafite/química , Poluentes Químicos da Água/química , Adsorção , Concentração de Íons de Hidrogênio , Hidróxidos , Cinética , Nanocompostos , Espectroscopia Fotoeletrônica , Polietilenoimina/química , Compostos de Potássio , Águas Residuárias
7.
Chemosphere ; 258: 127373, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32569957

RESUMO

The development of an adsorbent with high adsorption ability and favorable cyclic regeneration performance for the removal of nitrate residues from wastewater is a task of vital importance. To this end, polyacrylonitrile fiber (PANF) was modified with polyethyleneimine (PEI), and alkyl groups were then introduced around the active amine groups to prepare three polymer-based anion exchange fibers (PAN-PEI-3C, PAN-PEI-5C, and PAN-PEI-8C). The novel fibers were characterized using techniques such as scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The adsorption isotherms of the fibers were best fitted by the Langmuir model, and PAN-PEI-5C exhibited a higher adsorption amount of nitrate (31.32 mg/g) than the other adsorbents. The equilibrium was reached expeditiously (within 10 min), and both pseudo-first-order and pseudo-second-order models could well describe the adsorption kinetics. More attractively, the saturated PAN-PEI-5C could be eluted using a low-concentration (0.3 M) NaCl solution, without any sharp loss of adsorption amount for five consecutive cycles in the presence of dissolved organic matter (DOM). Furthermore, PAN-PEI-5C could effectively adsorb low-concentration nitrate from real secondary effluents in a fixed-bed column experiment. Our work provides a promising and low-cost material for the removal of nitrate residues in practical applications.


Assuntos
Resinas Acrílicas/química , Nitratos/análise , Polietilenoimina/química , Águas Residuárias/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Resinas de Troca de Ânions , Ânions , Cinética , Microscopia Eletrônica de Varredura , Nitratos/química , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/química
8.
Food Chem ; 328: 127131, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32485586

RESUMO

Carvacrol (CAR) is a natural bioactive compound with antioxidant and antimicrobial activity that is present in essential oils. The application of CAR in food preservation is hampered by its high volatility, low solubility in water, and susceptibility to light, heat and oxygen degradation. Polylactide (PLA) is an FDA-approved polymer derived from renewable resources. Controlled release of CAR from PLA nanoparticles (NPs) could improve its antimicrobial efficacy and storage. In this study, negatively charged CAR-NPs and positively charged polyethylenimine (PEI)-coated CAR-(PEI)NPs were formulated by nanoprecipitation methods and characterised by dynamic light scattering, electron microscopy, encapsulation efficiency, and drug loading capacity. The positively charged (PEI)NPs enhanced the in vitro antimicrobial activity of CAR against Escherichia coli, Listeria monocytogenes, Salmonella enterica and Staphylococcus aureus. Bacterial uptake, evaporation tests, release studies and NP stability after storage were assessed to provide evidence supporting CAR-(PEI)NPs as a potential nanocarrier for further development in food preservation.


Assuntos
Antibacterianos/farmacologia , Cimenos/farmacologia , Nanopartículas/química , Poliésteres/química , Antibacterianos/química , Cimenos/química , Cimenos/farmacocinética , Portadores de Fármacos/química , Escherichia coli/efeitos dos fármacos , Microbiologia de Alimentos , Listeria monocytogenes , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Polietilenoimina/química , Salmonella enterica/efeitos dos fármacos , Solubilidade , Staphylococcus aureus/efeitos dos fármacos
9.
Nat Commun ; 11(1): 2460, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424138

RESUMO

Fluorescent barcoding is a pivotal technique for the investigation of the microscale world, from information storage to the monitoring of dynamic biochemical processes. Using fluorescence lifetime as the readout modality offers more reproducible and quantitative outputs compared to conventional fluorescent barcoding, being independent of sample concentration and measurement methods. However, the use of fluorescence lifetime in this area has been limited by the lack of strategies that provide spatiotemporal manipulation of the coding process. In this study, we design a two-component photo-switchable nanogel that exhibits variable fluorescence lifetime upon photoisomerization-induced energy transfer processes through light irradiation. This remotely manipulated fluorescence lifetime property could be visually mapped using fluorescence lifetime imaging microscopy (FLIM), allowing selective storage and display of information at the microscale. Most importantly, the reversibility of this system further provides a strategy for minimizing the background influence in fluorescence lifetime imaging of live cells and sub-cellular organelles.


Assuntos
Luz , Microscopia de Fluorescência/métodos , Células A549 , Sobrevivência Celular , Transferência de Energia , Fluorescência , Humanos , Isomerismo , Mitocôndrias/metabolismo , Nanogéis/química , Polietilenoglicóis/química , Polietilenoimina/química , Polímeros/química , Frações Subcelulares
10.
Chemosphere ; 256: 127118, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32460162

RESUMO

Dye wastewater is harmful to the ecological environment because of its potential biological toxicity, teratogenicity, carcinogenicity, and mutagenicity. We fabricated a layered graphene oxide (GO) membrane through layer-by-layer (LBL) self-assembly. We used borate to crosslink with GO on a polyethyleneimine (PEI)-coated hydrolyzed polyacrylonitrile (hPAN) support. Fourier transform infrared (FTIR) spectrometry, Raman spectra, and x-ray photoelectron spectroscopy (XPS) confirmed the presence of a crosslinking reaction. The dynamic thermomechanical analysis (DMA) results indicated that the introduction of borate can significantly improve the mechanical properties of the membrane. The Young's modulus, ultimate tensile strength, and proportional limit of borate that was assembled twice as the outermost layer were increased by 110.81%, 62.37%, and 53.72%, respectively, as compared to those of a single-layered GO membrane. Moreover, the pure water fluxes of the layered GO membrane did not obviously decrease with an increase in the number of layers. The flux of the membrane with an outermost layer of borate was greater than that of the previous GO layer. The salt and dye rejection of the membranes was augmented with an increase in the number of layers. For the GO membrane assembled three times, rejection to methyl orange (MO), methylene blue (MB), NaCl, MgCl2, and MgSO4 reached 74.02%, 88.56%, 14.55%, 27.50%, and 41.95%, respectively. The use of borate as an inorganic crosslinker can avoid the environmental pollution caused by organic agents, and improve the mechanical properties as well as the filter capability of the layered GO membrane. Therefore, this study presents a novel method of membrane preparation for dye removal.


Assuntos
Compostos Azo/análise , Boratos/química , Grafite/química , Membranas Artificiais , Azul de Metileno/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Resinas Acrílicas/química , Filtração , Polietilenoimina/química , Propriedades de Superfície , Águas Residuárias/química
11.
Adv Clin Exp Med ; 29(4): 431-440, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32364686

RESUMO

BACKGROUND: Autogenous or allogenic bone transplantation is the main treatment for bone defects and nonunions. However, the shortcomings of autogenous or allogenic bone transplantation limit its wide application in clinical use. OBJECTIVES: This study investigated the effect of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with pOsterix (pOsx)/polyethylenimine (PEI) nanoparticles in repairing bone defects and explored its mechanism. MATERIAL AND METHODS: Poly(lactic-co-glycolic acid) microspheres loaded with pOsx/PEI nanoparticles were constructed. The Osx transfection effect was detected by fluorescence quantitative PCR and western blotting methods. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) and flow cytometry methods were used to detect cell proliferation. The collagen I (Col-1), osteopontin (OPN) and osteocalcin (OC) expression levels were detected using real-time polymerase chain reaction (RT-PCR) and western blotting methods. Bone defect model was constructed. Bone repair was detected using X-ray, hematoxylin and eosin (H&E) staining, and Mason staining methods. RESULTS: PLGA@pOsx/PEI has transfection effect both in vitro and in vivo, does not affect cell proliferation and is safe for cells. PLGA@pOsx/PEI could promote the expression of Col-1, OPN and OC in vitro and in vivo. PLGA@pOsx/PEI could promote osteogenesis in vivo. CONCLUSIONS: PLGA@pOsx/PEI with high Osx expression could promote the expression of OC, OPN, and COL-I. PLGA@pOsx/PEI can be used as a material for repairing bone defects and can promote bone formation. These results provide a theoretical and practical basis for its further clinical application.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Ácido Láctico/química , Nanopartículas , Polietilenoimina/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Western Blotting , Proliferação de Células/efeitos dos fármacos , Microesferas , Reação em Cadeia da Polimerase em Tempo Real
12.
Chemosphere ; 250: 126262, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32114342

RESUMO

As an attractive alternative to radioactive cesium removal, we introduced an adsorptive filtration method using a composite membrane consisting of potassium copper hexacyanoferrate (KCuHCF) and graphene-based support. Polyethyleneimine-grafted reduced graphene oxide (PEI-rGO), used as an immobilizing matrix, was effective not only in distributing KCuHCF inside the composite with the aid of abundant amino-functionality, but also in achieving high water flux by increasing the interlayer spacing of the laminar membrane structure. Due to the rapid and selective cesium adsorption properties of KCuHCF, the fabricated membrane was found to be effective in achieving complete removal of cesium ions under a high flux (over 500 L m-2 h-1), which is difficult in a conventional membrane utilizing the molecular sieving effect. This approach offers strong potential in the field of elimination of radionuclides that require rapid and complete decontamination.


Assuntos
Césio/química , Ferrocianetos/química , Grafite/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/química , Adsorção , Cobre/química , Filtração , Polietilenoimina/química , Potássio , Água
13.
Int J Nanomedicine ; 15: 1499-1515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189965

RESUMO

Purpose: Some chemotherapeutics have been shown to induce both the release of damage-associated molecular patterns (DAMPs) and the production of type I interferon (IFN-I), leading to immunogenic cell death (ICD). However, the standard chemotherapy drug for glioma, temozolomide (TMZ), cannot induce ICD as it cannot activate IFN-I signaling. Moreover, inefficient delivery of immunostimulants across the blood-brain barrier (BBB) is the main obstacle to overcome in order to induce local immune responses in the brain. Methods: A new oligonucleotide nanoformulation (Au@PP)/poly(I:C)) was constructed by coating gold nanoparticles (AuNPs) with methoxypolyethylene glycol (mPEG)-detachable (d)-polyethyleneimine (PEI) (Au@PP) followed by inducing the formation of electrostatic interactions with polyinosinic-polycytidylic acid (poly(I:C)). Intracranial GL261 tumor-bearing C57BL/6 mice were used to explore the therapeutic outcomes of Au@PP/poly(I:C) plus TMZ in vivo. The anti-tumor immune response in the brain induced by this treatment was analyzed by RNA sequencing and immunohistochemical analyses. Results: Au@PP/poly(I:C) induced IFN-I production after endocytosis into glioma cells in vitro. Additionally, Au@PP/poly(I:C) was efficiently accumulated in the glioma tissue after intranasal administration, which allowed the nanoformulation to enter the brain while bypassing the BBB. Furthermore, Au@PP/poly(I:C) plus TMZ significantly improved the overall survival of the tumor-bearing mice compared with group TMZ only. RNA sequencing and immunohistochemical analyses revealed efficient immune response activation and T lymphocyte infiltration in the Au@PP/poly(I:C) plus TMZ group. Conclusion: This study demonstrates that intranasal administration of Au@PP/poly(I:C) combined with TMZ induces ICD, thereby stimulating an in situ immune response to inhibit glioma growth.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/imunologia , Glioma/tratamento farmacológico , Glioma/imunologia , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/uso terapêutico , Administração Intranasal , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Feminino , Ouro/uso terapêutico , Humanos , Interferon Tipo I/metabolismo , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Poli I-C/síntese química , Poli I-C/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoimina/síntese química , Polietilenoimina/química , Análise de Sobrevida , Linfócitos T/efeitos dos fármacos , Temozolomida/farmacologia , Temozolomida/uso terapêutico
14.
Int J Nanomedicine ; 15: 1643-1659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210558

RESUMO

Purpose: Aseptic loosening is a major complication after total joint replacement. Reactive oxygen species generated by local tissue cells and liberated from implant surfaces have been suggested to cause implant failures. Surface modification of titanium (Ti)-based implants with proanthocyanidins (PAC) is a promising approach for the development of anti-oxidant defense mechanism to supplement the mechanical functions of Ti implants. In this study, a controlled PAC release system was fabricated on the surface of Ti substrates using the layer-by-layer (LBL) assembly. Materials and Methods: Polyethyleneimine (PEI) base layer was fabricated to enable layer-by-layer (LBL) deposition of hyaluronic acid/chitosan (HA/CS) multi-layers without or with the PAC. Surface topography and wettability of the fabricated HA/CS-PAC substrates were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FTIR) and contact angle measurement. PAC release profiles were investigated using drug release assays. MC3T3-E1 pre-osteoblast cells were used to assess the osteo-inductive effects of HA/CS-PAC substrates under conditions H2O2-induced oxidative stress in vitro. A rat model of femoral intramedullary implantation evaluated the osseo-integration and osteo-inductive potential of the HA/CS-PAC coated Ti implants in vivo. Results: SEM, AFM, FTIR and contact angle measurements verified the successful fabrication of Ti surfaces with multi-layered HA/CS-PAC coating. Drug release assays revealed controlled and sustained release of PAC over 14 days. In vitro, cell-based assays showed high tolerability and enhanced the osteogenic potential of MC3T3-E1 cells on HA/CS-PAC substrates when under conditions of H2O2-induced oxidative stress. In vivo evaluation of femoral bone 14 days after femoral intramedullary implantation confirmed the enhanced osteo-inductive potential of the HA/CS-PAC coated Ti implants. Conclusion: Multi-layering of HA/CS-PAC coating onto Ti-based surfaces by the LBL deposition significantly enhances implant osseo-integration and promotes osteogenesis under conditions of oxidative stress. This study provides new insights for future applications in the field of joint arthroplasty.


Assuntos
Antioxidantes/farmacologia , Osteogênese/efeitos dos fármacos , Proantocianidinas/farmacologia , Próteses e Implantes , Titânio/farmacologia , Animais , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quitosana/química , Liberação Controlada de Fármacos , Feminino , Ácido Hialurônico/química , Peróxido de Hidrogênio/farmacologia , Espaço Intracelular/metabolismo , Camundongos , Osseointegração/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Polietilenoimina/química , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Molhabilidade , Microtomografia por Raio-X
15.
Int J Nanomedicine ; 15: 1569-1583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210552

RESUMO

Background: MicroRNAs (miRNAs) are widely believed to be promising targets for oral squamous cell carcinoma (OSCC) gene therapy. miR-214 has been identified as a promoter of OSCC aggression and metastasis. Methods: Graphene oxide-polyethylenimine (GO-PEI) complexes were prepared and loaded with a miRNA inhibitor at different N/P ratios. The transfection efficiency of GO-PEI-inhibitor was tested in Cal27 and SCC9 cells. Moreover, the tumor inhibition ability of GO-PEI-inhibitor was measured in an OSCC xenograft mouse model by intratumoral injection. Results: Here, we show that a GO-PEI complex efficiently delivers a miR-214 inhibitor into OSCC cells and controls the intracellular release of the miR-214 inhibitor. These results indicate that the GO-PEI-miR-214 inhibitor complex efficiently inhibited cellular miR-214, resulting in a decrease in OSCC cell invasion and migration and an increase in cell apoptosis by targeting PTEN and p53. In the xenograft mouse model, the GO-PEI-miR-214 inhibitor complex significantly prevented tumor volume growth. Conclusion: This study indicates that functionalized GO-PEI with low toxicity has promising potential for miRNA delivery for the treatment of OSCC.


Assuntos
Antagomirs/administração & dosagem , Carcinoma de Células Escamosas/terapia , MicroRNAs/genética , Neoplasias Bucais/terapia , Transfecção/métodos , Animais , Apoptose/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Terapia Genética/métodos , Grafite/química , Humanos , Camundongos Endogâmicos BALB C , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , PTEN Fosfo-Hidrolase/genética , Polietilenoimina/química , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Int J Nanomedicine ; 15: 1397-1408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184594

RESUMO

Background: siRNA-mediated polo-like kinase 1 (PLK1) silencing has been proposed as a promising therapeutic method for multiple cancers. However, the clinic application of this method is still hindered by the low specific delivery of siPLK1 to desired tumor lesions. Herein, folate (FA)-modified and leucine-bearing polyethylenimine was successfully synthesized and showed excellent targeted silencing to folate receptor overexpressed cells. Materials and Methods: The condensation of siPLK1 by FA-N-Ac-L-Leu-PEI (NPF) was detected by the gel retardation assay. The targeted and silencing efficiency was evaluated by flow cytometry and confocal laser scanning microscope. The PLK1 expressions at gene or protein levels were detected by quantitative real-time PCR and Western blotting assay. Further impacts of the PLK1 silencing on cell viability, cell cycle, migration, and invasion were studied by MTT, colony formation, wound healing and transwell assays. Results: The NPF and siPLK1 could efficiently assemble to stable nanoparticles at a weight ratio of 3.0 and showed excellent condensation and protection effect. Owing to the FA-mediated targeted delivery, the uptake and silencing efficiency of NPF/siPLK1 to SGC-7901 cells was higher than that without FA modification. Moreover, NPF-mediated PLK1 silencing showed significant antitumor activity in vitro. The anti-proliferation effect of PLK1 silencing was induced via the mitochondrial-dependent apoptosis pathway with the cell cycle arrest of 45% at G2 phase and the apoptotic ratio of 28.3%. Conclusion: FA-N-Ac-L-Leu-PEI (NPF) could generate targeted delivery siPLK1 to FA receptor overexpressed cells and dramatically downregulate the expression of PLK1 expression.


Assuntos
Proteínas de Ciclo Celular/genética , Ácido Fólico/química , Técnicas de Transferência de Genes , Polietilenoimina/química , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias Gástricas/terapia , Células A549 , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Ácido Fólico/farmacologia , Inativação Gênica , Terapia Genética/métodos , Humanos , Leucina/química , Nanopartículas/química , RNA Interferente Pequeno/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
17.
Sci Total Environ ; 719: 137396, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32143096

RESUMO

Composite beads (APEI*), obtained by the controlled interaction of algal biomass with PEI, followed by ionotropic gelation and crosslinking processes using CaCl2/glutaraldehyde solution, constitute efficient supports for metal binding. The quaternization of algal/PEI beads (Q-APEI*) significantly increases the sorption properties of the composite beads (APEI*) for As(V). The materials are characterized by SEM/EDX, TGA, BET, elemental analysis, FTIR, XPS, and titration. The sorption of As(V) is studied in function of pH while sorption mechanism is discussed in function of metal speciation and surface characteristics of the sorbent. Optimum sorption occurs at pH close to 7. Fast uptake kinetics, correlated to textural properties are successfully fitted by pseudo-first order rate equation and the Crank equation (for resistance to intraparticle diffusion); equilibrium is reached with 45-60 min. The Langmuir equation finely fits sorption isotherms; maximum sorption capacity reaches 1.34 mmol As g-1. Arsenic can be completely eluted using 0.5 M CaCl2/0.5 M HCl solutions; the sorbent maintains high sorption and desorption efficiencies for a minimum of 5 cycles. The sorbent is tested for the removal of As(V) from mining effluents containing high concentration of iron and traces of zinc. At pH 3, the sorbent shows remarkable selectivity for As(V) over Fe. After controlling the initial pH to 5, a sorbent dosage of 2 g L-1 is sufficient for achieving the complete recovery of As(V) from mining effluent (corresponding to initial concentration of 1.295 mmol As L-1).


Assuntos
Polietilenoimina/química , Adsorção , Arsênico , Concentração de Íons de Hidrogênio , Cinética , Soluções , Estramenópilas , Água , Poluentes Químicos da Água
18.
Int J Nanomedicine ; 15: 749-760, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099363

RESUMO

Background: n-Butylidenephthalide (BP) has anti-tumor effects on glioblastoma. However, the limitation of BP for clinical application is its unstable structure. A polycationic liposomal polyethylenimine (PEI) and polyethylene glycol (PEG) complex (LPPC) has been developed to encapsulate BP for drug structure protection. The purpose of this study was to investigate the anti-cancer effects of the BP/LPPC complex on glioblastoma in vitro and in vivo. Methods: DBTRG-05MG tumor bearing xenograft mice were treated with BP and BP/LPPC and then their tumor sizes, survival, drug biodistribution were measured. RG2 tumor bearing F344 rats also treated with BP and BP/LPPC and then their tumor sizes by magnetic resonance imaging for evaluation blood-brain barrier (BBB) across and drug therapeutic effects. After treated with BP/LPPC in vitro, cell uptake, cell cycle and apoptotic regulators were analyzed for evaluation the therapeutic mechanism. Results: In athymic mice, BP/LPPC could efficiently suppress tumor growth and prolong survival. In F334 rats, BP/LPPC crossed the BBB and led to tumor shrinkage. BP/LPPC promoted cell cycle arrest at the G0/G1 phase and triggered the extrinsic and intrinsic cell apoptosis pathways resulting cell death. BP/LPPC also efficiently suppressed VEGF, VEGFR1, VEGFR2, MMP2 and MMP9 expression. Conclusion: BP/LPPC was rapidly and efficiently transported to the tumor area across the BBB and induced cell apoptosis, anti-angiogenetic and anti-metastatic effects in vitro and in vivo.


Assuntos
Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Anidridos Ftálicos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose , Barreira Hematoencefálica/patologia , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Lipossomos/química , Camundongos , Camundongos Nus , Anidridos Ftálicos/farmacologia , Polietilenoglicóis/química , Polietilenoimina/química , Ratos Endogâmicos F344 , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/patologia , Distribuição Tecidual/efeitos dos fármacos
19.
Int J Nanomedicine ; 15: 315-332, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021182

RESUMO

Purpose: The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system. Methods: In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field. Results: We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. Conclusion: The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury.


Assuntos
Astrócitos/fisiologia , Condroitina ABC Liase/metabolismo , Nanopartículas de Magnetita/uso terapêutico , Regeneração Nervosa/fisiologia , Células de Schwann/fisiologia , Animais , Astrócitos/citologia , Axônios/efeitos dos fármacos , Movimento Celular , Células Cultivadas , Condroitina ABC Liase/genética , Condroitina ABC Liase/farmacologia , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Feminino , Campos Magnéticos , Nanopartículas de Magnetita/química , Masculino , Regeneração Nervosa/efeitos dos fármacos , Polietilenoimina/química , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologia , Traumatismos da Medula Espinal/terapia
20.
J Nanobiotechnology ; 18(1): 34, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070342

RESUMO

BACKGROUND: The polymer-based drug/gene delivery is promising for the treatment of inherent or acquire disease, because of the polymer's structural flexibility, larger capacity for therapeutic agent, low host immunogenicity and less cost. Antisense therapy is an approach to fighting genetic disorders or infections using antisense oligonucleotides (AOs). Unfortunately, the naked AOs showed low therapeutic efficacy in vivo and in clinical trial due to their poor cellular uptake and fast clearance in bloodstream. In this study, a series of triazine-cored amphiphilic polymers (TAPs) were investigated for their potential to enhance delivery of AOs, 2'-O-methyl phosphorothioate RNA (2'-OMePS) and phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. RESULTS: TAPs significantly enhanced AO-induced exon-skipping in a GFP reporter-based myoblast and myotube culture system, and observed cytotoxicity of the TAPs were lower than Endoporter, Lipofectamine-2000 or PEI 25K. Application of optimized formulations of TAPs with AO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. The best ones for PMO and 2'-OMePS delivery have reached to 11-, 15-fold compared with the AO only in mdx mice, respectively. CONCLUSION: The study of triazine-cored amphiphilic polymers for AO delivery in vitro and in mdx mice indicated that the carrier's performances are related to the molecular size, compositions and hydrophilic-lipophilic balance (HLB) of the polymers, as well as the AO's structure. Improved exon-skipping efficiency of AOs observed in vitro and in mdx mice accompanied with low cytotoxicity demonstrated TAP polymers are potentials as safe and effective delivery carrier for gene/drug delivery.


Assuntos
Portadores de Fármacos/química , Oligonucleotídeos Antissenso/química , Polímeros/química , Triazinas/química , Animais , Permeabilidade da Membrana Celular , Distrofina/química , Feminino , Técnicas de Transferência de Genes , Terapia Genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Masculino , Camundongos Endogâmicos mdx , Estrutura Molecular , Morfolinos/química , Mioblastos/metabolismo , Polietilenoimina/química , Relação Estrutura-Atividade , Transfecção
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