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1.
Small ; 17(1): e2005086, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33284508

RESUMO

The epigenetic dysregulation and hypoxia are two important factors that drive tumor malignancy, and N6 -methyladenosine (m6 A) in mRNA is involved in the regulation of gene expression. Herein, a nanocatalyst OsSx -PEG (PEG = poly(ethylene glycol)) nanoparticles (NPs) as O2 modulator is developed to improve tumor hypoxia. OsSx -PEG NPs can significantly downregulate genes involved in hypoxia pathway. Interestingly, OsSx -PEG NPs elevate RNA m6 A methylation levels to cause the m6 A-dependent mRNA degradation of the hypoxia-related genes. Moreover, OsSx -PEG NPs can regulate the expression of RNA m6 A methyltransferases and demethylases. Finally, DOX@OsSx -PEG (DOX = doxorubicin; utilized as a model drug) NPs modulate tumor hypoxia and regulate mRNA m6 A methylation of hypoxia-related genes in vivo. As the first report about relationship between catalytic nanomaterials and RNA modifications, the research opens a new avenue for unveiling the underlying action mechanisms of hypoxia-modulating nanomaterials and shows potential of regulating RNA modification to overcome chemoresistance.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Doxorrubicina , Humanos , Hipóxia , Metilação , Polietilenoglicóis
2.
J Immunol ; 190(3): 987-96, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23267023

RESUMO

FcR specific for pentameric IgM (FCMR) is expressed at high levels by B cells. Although circulating IgM has profound effects on responses to pathogens, autoimmunity, and B cell homeostasis, the biologic consequences of its binding to FCMR are poorly understood. We interrogated FCMR contributions to B cell function by studying mice that lack FCMR. FCMR transcripts are expressed at different levels by various B cell subsets. FCMR-deficient mice have reduced numbers of developing B cells, splenic follicular and peritoneal B-2 cells, but increased levels of peritoneal B-1a cells and autoantibodies. After immunization, germinal center B cell and plasma cell numbers are increased. FCMR-deficient B cells are sensitive to apoptosis induced by BCR ligation. Our studies demonstrate that FCMR is required for B cell differentiation and homeostasis, the prevention of autoreactive B cells, and responsiveness to antigenic challenge.


Assuntos
Antígenos/imunologia , Linfócitos B/citologia , Imunoglobulina M/imunologia , Síndromes de Imunodeficiência/imunologia , Linfopoese/imunologia , Receptores Fc/imunologia , Animais , Formação de Anticorpos/imunologia , Apoptose/imunologia , Autoimunidade/imunologia , Linfócitos B/imunologia , Biopolímeros , Medula Óssea/imunologia , Medula Óssea/patologia , Centro Germinativo/patologia , Homeostase/imunologia , Imunização , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/patologia , Memória Imunológica , Camundongos , Camundongos Endogâmicos C57BL , Peritônio/imunologia , Peritônio/patologia , Plasmócitos/patologia , RNA Mensageiro/biossíntese , Receptores de Antígenos de Linfócitos B/imunologia , Receptores Fc/biossíntese , Receptores Fc/deficiência , Receptores Fc/genética , Baço/imunologia , Baço/patologia , Linfócitos T/imunologia
3.
Chemosphere ; 277: 130355, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34381285

RESUMO

Bisphenol A (BPA)-free plastic products are widely available. Transient BPA release has been reported in Tritan drinking bottles. This study assessed the effectiveness of common consumer washing methods in removing BPA contamination in Tritan bottles using both ELISA and HPLC-MS/MS assays. BPA release was detected in 2 out of 10 kinds of Tritan drinking bottles tested. Average BPA level was 0.493 µg/L in water samples from a type of Tritan kid drinking bottle following 24-hour incubation at room temperature, corresponding to a release rate of 0.015 ng/cm2/h. Of the common consumer cleaning methods identified in an informal survey, dishwashing was the most effective method that significantly reduced, even eliminated BPA release from the tested BPA-positive Tritan bottles, while rinsing with water and handwashing with soap and water were ineffective. The bioactivity of the leached BPA was confirmed using a rodent cardiac myocyte acute exposure model and an invertebrate 7-day exposure model. The BPA release is possibly the result of surface contamination in the manufacturing process. As a case study, our result may be informative for general consumer practice and for better quality control by the manufactures.


Assuntos
Compostos Benzidrílicos , Espectrometria de Massas em Tandem , Fenóis , Plásticos
4.
Int J Biol Macromol ; 193(Pt A): 293-299, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34656539

RESUMO

Cancer has become a serious disease threatening human health. To tackle this issue, developing the existing potent anticancer drugs is critical to reducing the time and cost associated with creating a new drug from scratch. Diethyldithiocarbamate (DDC) - an anticancer drug- has received considerable attention due to its selectivity and reactivity. In this study, we prepared a nanofibrous matrix from silk fibroin/polyethylene oxide loaded with diethyldithiocarbamate (DDC@SF/PEO) from an aqueous solution via an electrospinning process. Upon DDC incorporation, the nanofiber's diameter has increased from 450 nm (SF/PEO) to 1202 nm (DDC@SF/PEO) confirming the successful incorporation of DDC. Furthermore, the hydrophobicity of DDC@SF/PEO nanofibrous matrix was improved by turning SF structure from random coil (silk I) to ß-sheet (silk II) through ethanol vapor treatment. Biocompatibility of DDC@SF/PEO nanofibrous matrix on human normal cells (Wi-38) showed it was safe and the apoptosis-mediated anticancer activity of DDC was enhanced. Thus, loading DDC on SF/PEO nanofibrous matrix is the key descriptor for enhanced anticancer efficacy of DDC. Considering the all-aqueous and simplistic process, the DDC@SF/PEO nanofibrous matrix could be a promising candidate for cancer treatment applications.


Assuntos
Ditiocarb/química , Neoplasias/tratamento farmacológico , Polietilenoglicóis/química , Seda/química , Engenharia Tecidual/métodos , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Alicerces Teciduais
5.
Biomed Mater ; 16(6)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34547733

RESUMO

Electrospinning represents the simplest approach to fabricate nanofiber scaffolds that approximate the heterogeneous fibrous structure of the meniscus. More effort is needed to understand the relationship between scaffold properties and cell responses to determine the appropriate scaffolds supporting meniscus tissue repair and regeneration. In this study, we investigate the influence of nanofiber configuration of electrospun scaffolds on phenotype and matrix production of meniscus cells, as well as on scaffold degradation behaviors and biocompatibility. Twisting electrospun nanofibers into yarns not only recapitulates the major collagen bundles of the meniscus but also increases the pore size and porosity of resultant scaffolds. The yarn scaffold significantly regulated expression levels of meniscus-associated genes and promoted extracellular matrix production compared with conventional electrospun scaffolds with random or aligned nanofiber orientation. Additionally, the yarn scaffold allowed considerable cell infiltration and experienced faster degradation and tissue remodeling upon subcutaneous implantation in a rat model. These results suggest that nanofiber configuration dictates cell interactions, scaffold degradation and integration with host tissue, providing design parameters of porosity and pore size of electrospun scaffolds toward meniscus repair.


Assuntos
Matriz Extracelular Descelularizada , Menisco/citologia , Nanofibras/química , Alicerces Teciduais/química , Animais , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/farmacologia , Técnicas Eletroquímicas , Ratos , Engenharia Tecidual
6.
J Mater Chem B ; 9(17): 3727-3744, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33904568

RESUMO

Bacterial infections cause severe secondary damage to wounds and hinder wound healing processes. We prepared magnesium oxide (MgO) nanoparticle-incorporated nanofibrous membranes by electrospinning and investigated their potential for wound dressing and fighting bacterial infection. MgO-Incorporated membranes possessed good elasticity and flexibility similar to native skin tissue and were hydrophilic, ensuring comfortable contact with wound beds. The cytocompatibility of membranes was dependent on the amounts of incorporated MgO nanoparticles: lower amounts promoted while higher amounts suppressed the proliferation of fibroblasts, endothelial cells, and macrophages. The antibacterial capacity of membranes was proportional to the amounts of incorporated MgO nanoparticles and they inhibited more than 98% E. coli, 90% S. aureus, and 94% S. epidermidis. MgO nanoparticle-incorporated membranes effectively suppressed bacterial infection and significantly promoted the healing processes of infected full-thickness wounds in a rat model. Subcutaneous implantation demonstrated that the incorporation of MgO nanoparticles into electrospun membranes elevated their bioactivity as evidenced by considerable cell infiltration into their dense nanofiber configuration and enhanced the remodeling of implanted membranes. This study highlights the potential of MgO-incorporated electrospun membranes in preventing bacterial infections of wounds.


Assuntos
Antibacterianos/química , Infecções Bacterianas/prevenção & controle , Materiais Biocompatíveis/química , Óxido de Magnésio/química , Nanopartículas Metálicas/química , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Bandagens , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Gelatina/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Interações Hidrofóbicas e Hidrofílicas , Óxido de Magnésio/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Nanofibras/química , Poliésteres/química , Implantação de Prótese , Ratos Sprague-Dawley , Pele , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Engenharia Tecidual
7.
Int J Mol Sci ; 11(9): 3529-39, 2010 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-20957110

RESUMO

Chitosan, a naturally occurring polysaccharide with abundant resources, has been extensively exploited for various biomedical applications, typically as wound dressings owing to its unique biocompatibility, good biodegradability and excellent antibacterial properties. In this work, composite nanofibrous membranes of chitosan (CS) and silk fibroin (SF) were successfully fabricated by electrospinning. The morphology of electrospun blend nanofibers was observed by scanning electron microscopy (SEM) and the fiber diameters decreased with the increasing percentage of chitosan. Further, the mechanical test illustrated that the addition of silk fibroin enhanced the mechanical properties of CS/SF nanofibers. The antibacterial activities against Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) were evaluated by the turbidity measurement method; and results suggest that the antibacterial effect of composite nanofibers varied on the type of bacteria. Furthermore, the biocompatibility of murine fibroblast on as-prepared nanofibrous membranes was investigated by hematoxylin and eosin (H&E) staining and MTT assays in vitro, and the membranes were found to promote the cell attachment and proliferation. These results suggest that as-prepared chitosan/silk fibroin (CS/SF) composite nanofibrous membranes could be a promising candidate for wound healing applications.


Assuntos
Antibacterianos/química , Bandagens , Materiais Biocompatíveis/química , Quitosana/química , Fibroínas/química , Nanofibras/química , Animais , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Fibroínas/farmacologia , Camundongos , Staphylococcus aureus/efeitos dos fármacos
8.
Appl Biochem Biotechnol ; 191(4): 1624-1637, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32198603

RESUMO

This study aims to develop scaffold for transdermal drug delivery method (TDDM) using electrospinning technique from polyvinyl alcohol (PVA) and hydroxyethylcellulose (HEC). The fluorescein isothiocyanate (FITC) loaded on ethosomes (FITC@Eth) was used as a drug model. The prepared PVA/HEC/FITC@Eth scaffold was characterized via scanning electron microscope (SEM) that show morphology change by adding FITC@Eth. Also, Fourier transform infrared spectroscopy (FTIR), mechanical properties, X-ray diffraction (XRD), thermal gravimetric (TGA) analysis show that the addition of FITC@Eth to PVA/HEC does not change the scaffold properties. Franz diffusion cells were used for in vitro skin permeation experiments using rat dorsal skins. The FITC@Eth penetration was better than that of free FITC due to the presence of ethosome which enhance the potential skin targeting. In conclusion, the prepared PVA/HEC/FITC@Eth scaffold can serve as a promising transdermal scaffold for sustained FITC release.


Assuntos
Celulose/análogos & derivados , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Álcool de Polivinil/química , Administração Cutânea , Animais , Celulose/química , Química , Difusão , Fluoresceína-5-Isotiocianato , Permeabilidade , Polímeros/química , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico , Termogravimetria , Difração de Raios X
9.
Acta Biomater ; 108: 207-222, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32251784

RESUMO

Biomaterial-based membranes represent a promising therapeutic option for periodontal diseases. Although conventional periodontal membranes function greatly in preventing the ingrowth of both fibroblasts and epithelial cells as well as connective tissues, they are not capable of promoting periodontal tissue regeneration. Here, we report a multifunctional periodontal membrane prepared by electrospinning biodegradable polymers with magnesium oxide nanoparticles (nMgO). nMgO is a light metal-based nanoparticle with high antibacterial capacity and can be fully resorbed in the body. Our results showed that incorporating nMgO into poly(L-lactic acid) (PLA)/gelatin significantly improved the overall properties of membranes, including elevated tensile strength to maintain structural stability and adjusted degradation rate to fit the time window of periodontal regeneration. Acidic degradation products of PLA were neutralized by alkaline ions from nMgO hydrolysis, ameliorating pH microenvironment beneficial for cell proliferation. In vitro studies demonstrated considerable antibacterial and osteogenic properties of nMgO-incorporated membranes that are highly valuable for periodontal regeneration. Further investigations in a rat periodontal defect model revealed that nMgO-incorporated membranes effectively guided periodontal tissue regeneration. Taken together, our data indicate that nMgO-incorporated membranes might be a promising therapeutic option for periodontal regeneration. STATEMENT OF SIGNIFICANCE: Traditional clinical treatments of periodontal diseases largely focus on the management of the pathologic processes, which cannot effectively regenerate the lost periodontal tissue. GTR, a classic method for periodontal regeneration, has shown promise in clinical practice. However, the current membranes might not fully fulfill the criteria of ideal membranes. Here, we report bioabsorbable nMgO-incorporated nanofibrous membranes prepared by electrospinning to provide an alternative for the clinical practice of GTR. The membranes not only function greatly as physical barriers but also exhibit high antibacterial and osteoinductive properties. We therefore believe that this study will inspire more practice work on the development of effective GTR membranes for periodontal regeneration.


Assuntos
Regeneração Tecidual Guiada Periodontal , Nanofibras , Animais , Materiais Biocompatíveis/farmacologia , Membranas Artificiais , Periodonto , Ratos
10.
J Mater Sci Mater Med ; 20(11): 2285-94, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19572107

RESUMO

The aim of this study is to investigate an innovative tissue engineering scaffold with a controllable drug-releasing capability. The hypothesis is that the nanofibers fabricated by coaxial electrospinning could encapsulate and release sustainedly Tetracycline Hydrochloride (TCH). To testify the hypothesis, nanofibers were prepared by coaxial electrospinning from Poly(L-lactid-co-epsilon-caprolactone) [PLLACL]/2,2,2-Frifluoroethanol (TFE) solutions (as the shell solutions) and TCH/TFE solutions (as the core solutions). In addition, nanofibers of PLLACL-blend-TCH were also prepared as the control by mix electrospinning. The relationship between fibers morphologies and processed conditions in electrospinning were investigated. TCH release behaviors from the nanofibrous mats were studied. The antibacterial properties of aforementioned nanofibers were detected by the Escherichia coli growth-inhibiting tests. The results indicated that the nanofibers prepared by coaxial-electrospinning had the desired and controllable TCH encapsulation/release profile; thus, it could be utilized as both a drug encapsulation/release vehicle and a tissue engineering scaffold.


Assuntos
Biodegradação Ambiental , Nanofibras/química , Poliésteres/química , Tetraciclina/química , Animais , Antibacterianos/química , Materiais Biocompatíveis/química , Desenho de Fármacos , Desenho de Equipamento , Escherichia coli/metabolismo , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura/métodos , Peso Molecular , Nanotecnologia/métodos , Polímeros/química , Solventes/química , Fatores de Tempo , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Trifluoretanol/química
11.
Nanomedicine (Lond) ; 14(18): 2395-2408, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31456475

RESUMO

Aim: Multidrug resistance is the main reason for the failure of chemotherapy during the treatment of the tumor. To overcome multidrug resistance, this study attempts to develop a novel transdermal drug-delivery system (TDDS) loading cytotoxic drug and chemosensitizer. Materials & methods: The polyethylenimine-modified ethosomes (Eth-PEI) and sodium cholate-modified ethosomes (Eth-SC) were firstly fabricated, and then a novel TDDS based on the carriers complex of Eth-PEI/Eth-SC was prepared by electrostatic interaction and evaluated both in vitro and in vivo. Results: The Eth-PEI/Eth-SC showed the excellent antitumor effect on treating melanoma, using doxorubicin and curcumin as the cytotoxic drug and chemosensitizer, respectively. Conclusion: The as-prepared TDDS composed of Eth-PEI/Eth-SC loading multidrug is an effective means for treating melanoma.


Assuntos
Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Melanoma Experimental/tratamento farmacológico , Polietilenoimina/química , Administração Cutânea , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Curcumina/farmacocinética , Curcumina/uso terapêutico , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Absorção Cutânea , Colato de Sódio/química
12.
Colloids Surf B Biointerfaces ; 161: 94-102, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29054048

RESUMO

Surgical adhesive is the optimal candidate for the replacement of traditional mechanical wound closure. In our paper, mussel adhesive proteins inspired hydrogel adhesive was prepared with 3, 4-dihydroxyphyenylanine acrylamide (DOPA-AA), poly (ethylene glycol) diacrylate (PEGDAA) and thiolated chitosan (CSS) by UV irradiation. DOPA-AA, containing catechol group and vinyl group, was successful synthesized and characterized by FTIR and 1HNMR. The gelation time, equilibrium water content, degradation, materials properties and adhesive strength of the hydrogels were studied. We found that the gelation time was retarded and the materials mechanical strength was decreased because of the inhibitory effect of catechol group. Equilibrium water content was slightly affect by the increasing concentration of DOPA-AA (1-5%). Nevertheless, catechol group can remarkably improve the adhesive properties because of the complex and durable interactions of the hydrogel, especially, the interaction between the thiol group of CSS and catechol group of DOPA-AA, which also greatly slowed down the degradation of the adhesive hydrogels. CSS and DOPA-AA was introduced to ensure the adhesive properties, DOPA-AA lend the adhesive nature to hydrogel and CSS can protect the catechol group from oxidation and enhance durable adhesion. Moreover, cytotoxicity of the resulting hydrogels showed that the L929 cell viability was weaken, it mostly probably induced by the catechol oxidation.


Assuntos
Adesivos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Polímeros/química , Proteínas/química , Acrilamidas/química , Adesivos/farmacologia , Animais , Bivalves/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Quitosana/metabolismo , Di-Hidroxifenilalanina/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Camundongos , Processos Fotoquímicos/efeitos da radiação , Polietilenoglicóis/química , Compostos de Sulfidrila/química , Raios Ultravioleta
13.
Int J Nanomedicine ; 13: 7003-7018, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464455

RESUMO

INTRODUCTION: The fast degradation of vascular graft and the infiltration of smooth muscle cells (SMCs) into the vascular graft are considered to be critical for the regeneration of functional neo-vessels. In our previous study, a novel dual phase separation technique was developed to one-pot prepare macroporous nanofibrous poly(L-lactic acid) (PLLA)/poly(ε-caprolactone) (PCL) vascular scaffold by phase separating the immiscible polymer blend. However, the slow degradation of PLLA/PCL limited cell infiltration. Herein, we hypothesized that poly(lactic-co-glycolic acid) (PLGA) would be miscible with PLLA but immiscible with PCL. Then, PLGA can be introduced into the PLLA/PCL blend to fabricate macroporous nanofibrous scaffold with improved biodegradability by using dual phase separation technique. MATERIALS AND METHODS: The miscibility of PLGA with PLLA and PCL was evaluated. Then, the PLLA/PLGA/PCL scaffold was prepared by dual phase separation technique. The prepared scaffolds were characterized in terms of the morphology, in vitro degradation, mechanical properties, and cells' infiltration and viability for human vascular SMCs (HVSMCs). Finally, platelet-derived growth factor-BB (PDGF-BB) was immobilized on the scaffold and its effect on the bioactivity of HVSMCs was studied. RESULTS: PLGA is miscible with PLLA but immiscible with PCL as hypothesized. The addition of PLGA enlarged the pore size and improved the biodegradability of composite scaffold. Notably, PLLA/PLGA/PCL scaffold with the blend ratio of 30:40:30 possessed improved pore interconnectivity for cells' infiltration and enough mechanical properties. Moreover, HVSMCs could grow and infiltrate into this scaffold, and surface modification with PDGF-BB on the nanofibrous scaffold enhanced HVSMCs migration and proliferation. CONCLUSION: This study provides a strategy to expand dual phase separation technique into utilizing ternary even multinary polymer blend to fabricate macroporous nanofibrous scaffold with improved physicochemical properties. The prepared PLLA/PLGA/PCL scaffold would be promising for the regeneration of functional tunica media in vascular tissue engineering.


Assuntos
Materiais Biocompatíveis/farmacologia , Vasos Sanguíneos/fisiologia , Miócitos de Músculo Liso/citologia , Nanofibras/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Becaplermina/farmacologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porosidade , Implantação de Prótese , Ratos Sprague-Dawley , Tela Subcutânea/efeitos dos fármacos , Resistência à Tração
14.
Theranostics ; 8(5): 1361-1375, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29507626

RESUMO

PURPOSE: Osteosarcoma is the most common primary bone cancer and is notorious for pulmonary metastasis, representing a major threat to pediatric patients. An effective drug targeting osteosarcoma and its lung metastasis is urgently needed. DESIGN: In this study, a sarcoma-targeting peptide-decorated disulfide-crosslinked polypeptide nanogel (STP-NG) was exploited for enhanced intracellular delivery of shikonin (SHK), an extract of a medicinal herb, to inhibit osteosarcoma progression with minimal systemic toxicity. RESULTS: The targeted, loaded nanogel, STP-NG/SHK, killed osteosarcoma cells by inducing RIP1- and RIP3-dependent necroptosis in vitro. Necroptosis is a novel cell death form that could be well adapted as an efficient antitumor strategy, the main obstacle of which is its high toxicity. After intravenous injection, STP-NG/SHK efficiently suppressed tumor growth and reduced pulmonary metastasis, offering greater tumor necrosis and higher RIP1 and RIP3 upregulation compared to free SHK or untargeted NG/SHK in vivo. Additionally, the treatment with NG/SHK or STP-NG/SHK showed minimal toxicity to normal organs, suggesting low systemic toxicity compared to free SHK. CONCLUSION: The STP-guided intracellular drug delivery system using the necroptosis mechanism showed profound anti-osteosarcoma activity, especially eliminated lung metastasis in vivo. This drug formulation may have great potential for treatment of osteosarcoma.


Assuntos
Apoptose , Neoplasias Pulmonares/secundário , Naftoquinonas/administração & dosagem , Osteossarcoma/patologia , Peptídeos/química , Polietilenoglicóis/química , Polietilenoimina/química , Sarcoma/patologia , Regulação para Cima , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Espaço Intracelular/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Camundongos Nus , Nanogéis , Naftoquinonas/efeitos adversos , Naftoquinonas/uso terapêutico , Necrose , Osteossarcoma/tratamento farmacológico , Polietilenoglicóis/efeitos adversos , Polietilenoimina/efeitos adversos , Distribuição Tecidual
15.
Colloids Surf B Biointerfaces ; 139: 156-63, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26707696

RESUMO

Silk fibroin (SF) from Bombyx mori has an excellent biocompatibility and thus be widely applied in the biomedical field. Recently, various SF-based composite nanofibers have been developed for more demanding applications. Additionally, grape seed extract (GSE) has been demonstrated to be powerful on antioxidation. In the present study, we dedicate to fabricate a GSE-loaded SF/polyethylene oxide (PEO) composite nanofiber by green electrospinning. Our results indicated the successful loading of GSE into the SF/PEO composite nanofibers. The introduction of GSE did not affect the morphology of the SF/PEO nanofibers and GSE can be released from the nanofibers with a sustained manner. Furthermore, comparing with the raw SF/PEO nanofibrous mats, the GSE-loaded SF/PEO nanofibrous mats significantly enhanced the proliferation of the skin fibroblasts and also protected them against the damage from tert-butyl hydroperoxide-induced oxidative stress. All these findings suggest a promising potential of this novel GSE-loaded SF/PEO composite nanofibrous mats applied in skin care, tissue regeneration and wound healing.


Assuntos
Antioxidantes/farmacologia , Materiais Biocompatíveis/síntese química , Fibroínas/química , Extrato de Sementes de Uva/farmacologia , Nanocompostos/química , Nanofibras/química , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Materiais Biocompatíveis/farmacologia , Bombyx , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Técnicas Eletroquímicas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Extrato de Sementes de Uva/química , Extrato de Sementes de Uva/metabolismo , Química Verde , Camundongos , Oxidantes/farmacologia , Polietilenoglicóis/química , Pele/citologia , Pele/efeitos dos fármacos , terc-Butil Hidroperóxido/farmacologia
16.
Dalton Trans ; 43(31): 11834-42, 2014 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-24957865

RESUMO

This paper presents a facile method for the fabrication of uniform hollow mesoporous silica nanoparticles (HMSNs) with tunable shell thickness and pore size. In this method, a series of amphiphilic block copolymers of polystyrene-b-poly (acrylic acid) (PS-b-PAA) with different hydrophobic block (PS) lengths were first synthesized via atom transfer radical polymerization (ATRP). The as-synthesized PS-b-PAA and cetyltrimethylammonium bromide (CTAB) were subsequently used as co-templates to fabricate HMSNs. This approach allows the control of shell thickness and pore size distribution of the synthesized HMSNs simply by changing the amounts of PS-b-PAA and CTAB, respectively. In vitro cytotoxicity and hemolysis assays demonstrated that the synthesized HMSNs had a low and shell thickness-dependent cytotoxicity and hemolytic activity. Therefore, these HMSNs have great potential for biomedical applications due to their good biocompatibility and ease of synthesis.


Assuntos
Acrilatos/química , Nanopartículas/química , Poliestirenos/química , Dióxido de Silício/química , Sobrevivência Celular/efeitos dos fármacos , Cetrimônio , Compostos de Cetrimônio/química , Eritrócitos/efeitos dos fármacos , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Porosidade , Dióxido de Silício/farmacologia , Tensoativos/química
17.
Int J Biol Macromol ; 56: 49-56, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23396066

RESUMO

In the present study, we reported fabrication and skin benefit of a novel vitamin E (VE)-loaded silk fibroin (SF) nanofibrous mats. RRR-α-Tocopherol polyethylene glycol 1000 succinate (VE TPGS), a water-soluble derivative of VE, was incorporated into SF nanofiber successfully by aqua solution electrospinning for the first time. Morphology of the composite nanofibers changed with the different amount of VE TPGS: a ribbon-like shape for lower loading dose of VE TPGS, while a round shape for higher loading dose (more than 4% (wt/wt) based on the weight of SF). After treated with 75% (v/v) ethanol vapor, the composite nanofibrous mats showed an excellent water-resistant ability. In vitro study disclosed a sustained release behavior of VE TPGS disassociated from the nanofibrous mats. The mouse skin fibroblasts (L929 cells) cultured on the VE-loaded SF nanofibrous mats spread and proliferated much better than on cover slips. Moreover, the incorporation of VE TPGS was found strengthening the ability of SF nanofibrous mats on protecting the cells against oxidation stress induced by tert-butyl hydroperoxide. Our data presented impressive skin benefits of this VE-loaded SF nanofibrous mats, suggesting a promising applicative potential of this novel product on personal skin care, tissue regeneration and other related area.


Assuntos
Fibroínas/farmacologia , Química Verde/métodos , Nanofibras/química , Higiene da Pele/métodos , Vitamina E/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/ultraestrutura , Fibroínas/química , Camundongos , Micelas , Nanofibras/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Polietilenoglicóis , Polímeros/química , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier , Succinatos/farmacologia , Vitamina E/análogos & derivados , Difração de Raios X , terc-Butil Hidroperóxido/farmacologia
18.
J Biomed Mater Res A ; 97(3): 339-47, 2011 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-21465642

RESUMO

Coelectrospinning of native proteins and elastic synthetic polymers is an attractive technique to fabricate hybrid fibrous scaffolds that combine the bioactivity and mechanical features of each material component. In this study, hybrid fibrous scaffolds composed of synthetic P(LLA-CL) elastomeric and naturally derived fibrinogen protein were fabricated and characterized for their bioactive and physiochemical properties. Fiber diameters of hybrid scaffolds increased with increasing P(LLA-CL) content, and the shape of fibers changed from cylindrical shape on pure polymer scaffolds to flat structure on hybrid scaffolds. Characterizations of ATR-FTIR, XRD, and thermal properties indicated that the hybrid scaffolds contain two different phases, one composed of pure fibrinogen and the other corresponding to a mixture of fibrinogen and P(LLA-CL), and no obvious chemical reaction takes place between two components. The hybrid fibrous scaffolds showed tailorable degradation rates than pure P(LLA-CL) and higher mechanical properties than pure fibrinogen, and both tensile strength and breaking strain increased with increasing P(LLA-CL) content. In Vitro studies revealed that L929 cells on hybrid scaffolds achieved relatively higher level of cell attachment after 12 h of culture and significant increased cell proliferation rate after 7 days of culture, when compared with pure fibrinogen and P(LLA-CL) scaffolds, and the cells exhibited a spreading polygonal shape on the hybrid fibrous surfaces compared to a round shape on surfaces of pure polymer scaffolds. Therefore, the fibrinogen/P(LLA-CL) hybrid fibrous scaffolds possess the combined benefits of each individual component, which make it capable as scaffolds for soft tissue reconstruction.


Assuntos
Fibrinogênio/química , Fibroblastos/citologia , Poliésteres/química , Alicerces Teciduais/química , Animais , Adesão Celular , Linhagem Celular , Proliferação de Células , Camundongos , Nanoestruturas/química , Resistência à Tração , Engenharia Tecidual/métodos
19.
Int J Biol Macromol ; 48(3): 474-81, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21255605

RESUMO

The development of three-dimensional (3-D) scaffolds with highly open porous structure is one of the most important issues in tissue engineering. In this study, 3-D macroporous gelatin/hyaluronic acid (GE/HA) hybrid scaffolds with varying porous morphology were prepared by freeze-drying their blending solutions and subsequent chemical crosslinking by using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The resulting scaffolds were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Their swelling, in vitro degradation properties and compressive strength were also investigated. To evaluate in vitro cytocompatibility of scaffolds, mouse L929 fibroblasts were seeded onto the scaffolds for cell morphology and cell viability studies. It was found that the porous structure of scaffolds can be tailored by varying the ratios of gelatin to HA, both the swelling ratios and degradation rate increased with the increase of HA content in hybrid scaffolds, and crosslinking the scaffolds with EDC improved the degradation resistance of the scaffold in culture media and increased the mechanical strength of scaffolds. The in vitro results revealed that the prepared scaffolds do not induce cytotoxic effects and suitable for cell growth, especially in the case of scaffolds with higher gelatin content. The combined results of the physicochemical and biological studies suggested that the developed GE/HA hybrid scaffolds exhibit good potential and biocompatibility for soft tissue engineering applications.


Assuntos
Gelatina , Ácido Hialurônico , Engenharia Tecidual , Alicerces Teciduais , Animais , Materiais Biocompatíveis/metabolismo , Adesão Celular , Linhagem Celular , Sobrevivência Celular , Força Compressiva , Gelatina/química , Gelatina/metabolismo , Ácido Hialurônico/química , Ácido Hialurônico/metabolismo , Camundongos , Microscopia Eletrônica de Varredura , Porosidade
20.
Colloids Surf B Biointerfaces ; 79(2): 315-25, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20471809

RESUMO

Collagen functionalized thermoplastic polyurethane nanofibers (TPU/collagen) were successfully produced by coaxial electrospinning technique with a goal to develop biomedical scaffold. A series of tests were conducted to characterize the compound nanofiber and its membrane in this study. Surface morphology and interior structure of the ultrafine fibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM), whereas the fiber diameter distribution was also measured. The crosslinked membranes were also characterized by SEM. Porosities of different kinds of electrospun mats were determined. The surface chemistry and chemical composition of collagen/TPU coaxial nanofibrous membranes were verified by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectrometry (FTIR). Mechanical measurements were carried out by applying tensile test loads to samples which were prepared from electrospun ultra fine non-woven fiber mats. The coaxial electrospun nanofibers were further investigated as a promising scaffold for PIECs culture. The results demonstrated that coaxial electrospun composite nanofibers had the characters of native extracellular matrix and may be used effectively as an alternative material for tissue engineering and functional biomaterials.


Assuntos
Colágeno/farmacologia , Nanofibras/química , Plásticos/farmacologia , Poliuretanos/farmacologia , Temperatura , Engenharia Tecidual/métodos , Animais , Sobrevivência Celular/efeitos dos fármacos , Elementos Químicos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/ultraestrutura , Microscopia de Força Atômica , Nanofibras/ultraestrutura , Espectroscopia Fotoeletrônica , Porosidade/efeitos dos fármacos , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície/efeitos dos fármacos , Sus scrofa , Resistência à Tração/efeitos dos fármacos
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