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1.
J Nanobiotechnology ; 19(1): 453, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34963449

RESUMO

BACKGROUND: The interactions between nanoparticles (NPs) and plasma proteins form a protein corona around NPs after entering the biological environment, which provides new biological properties to NPs and mediates their interactions with cells and biological barriers. Given the inevitable interactions, we regard nanoparticle‒protein interactions as a tool for designing protein corona-mediated drug delivery systems. Herein, we demonstrate the successful application of protein corona-mediated brain-targeted nanomicelles in the treatment of glioma, loading them with paclitaxel (PTX), and decorating them with amyloid ß-protein (Aß)-CN peptide (PTX/Aß-CN-PMs). Aß-CN peptide, like the Aß1-42 peptide, specifically binds to the lipid-binding domain of apolipoprotein E (ApoE) in vivo to form the ApoE-enriched protein corona surrounding Aß-CN-PMs (ApoE/PTX/Aß-CN-PMs). The receptor-binding domain of the ApoE then combines with low-density lipoprotein receptor (LDLr) and LDLr-related protein 1 receptor (LRP1r) expressed in the blood-brain barrier and glioma, effectively mediating brain-targeted delivery. METHODS: PTX/Aß-CN-PMs were prepared using a film hydration method with sonication, which was simple and feasible. The specific formation of the ApoE-enriched protein corona around nanoparticles was characterized by Western blotting analysis and LC-MS/MS. The in vitro physicochemical properties and in vivo anti-glioma effects of PTX/Aß-CN-PMs were also well studied. RESULTS: The average size and zeta potential of PTX/Aß-CN-PMs and ApoE/PTX/Aß-CN-PMs were 103.1 nm, 172.3 nm, 7.23 mV, and 0.715 mV, respectively. PTX was efficiently loaded into PTX/Aß-CN-PMs, and the PTX release from rhApoE/PTX/Aß-CN-PMs exhibited a sustained-release pattern in vitro. The formation of the ApoE-enriched protein corona significantly improved the cellular uptake of Aß-CN-PMs on C6 cells and human umbilical vein endothelial cells (HUVECs) and enhanced permeability to the blood-brain tumor barrier in vitro. Meanwhile, PTX/Aß-CN-PMs with ApoE-enriched protein corona had a greater ability to inhibit cell proliferation and induce cell apoptosis than taxol. Importantly, PTX/Aß-CN-PMs exhibited better anti-glioma effects and tissue distribution profile with rapid accumulation in glioma tissues in vivo and prolonged median survival of glioma-bearing mice compared to those associated with PMs without the ApoE protein corona. CONCLUSIONS: The designed PTX/Aß-CN-PMs exhibited significantly enhanced anti-glioma efficacy. Importantly, this study provided a strategy for the rational design of a protein corona-based brain-targeted drug delivery system. More crucially, we utilized the unfavorable side of the protein corona and converted it into an advantage to achieve brain-targeted drug delivery.


Assuntos
Antineoplásicos/administração & dosagem , Apolipoproteínas E/administração & dosagem , Encéfalo/efeitos dos fármacos , Glioma/tratamento farmacológico , Nanopartículas/administração & dosagem , Coroa de Proteína , Peptídeos beta-Amiloides/administração & dosagem , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/farmacocinética , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apolipoproteínas E/química , Apolipoproteínas E/farmacocinética , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Glioma/metabolismo , Humanos , Camundongos , Micelas , Nanopartículas/química , Paclitaxel/administração & dosagem , Paclitaxel/química , Paclitaxel/farmacocinética , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacocinética , Poliésteres/administração & dosagem , Poliésteres/química , Poliésteres/farmacocinética , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Coroa de Proteína/química
2.
Proc Natl Acad Sci U S A ; 115(2): E263-E272, 2018 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-29279393

RESUMO

Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement. Here, we report a simple cell encapsulation design that is readily scalable and conveniently retrievable. The key to this design was to engineer a highly wettable, Ca2+-releasing nanoporous polymer thread that promoted uniform in situ cross-linking and strong adhesion of a thin layer of alginate hydrogel around the thread. The device provided immunoprotection of rat islets in immunocompetent C57BL/6 mice in a short-term (1-mo) study, similar to neat alginate fibers. However, the mechanical property of the device, critical for handling and retrieval, was much more robust than the neat alginate fibers due to the reinforcement of the central thread. It also had facile mass transfer due to the short diffusion distance. We demonstrated the therapeutic potential of the device through the correction of chemically induced diabetes in C57BL/6 mice using rat islets for 3 mo as well as in immunodeficient SCID-Beige mice using human islets for 4 mo. We further showed, as a proof of concept, the scalability and retrievability in dogs. After 1 mo of implantation in dogs, the device could be rapidly retrieved through a minimally invasive laparoscopic procedure. This encapsulation device may contribute to a cellular therapy for T1D because of its retrievability and scale-up potential.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/fisiologia , Alginatos , Animais , Diabetes Mellitus Experimental/terapia , Dimetilformamida , Cães , Ácido Glucurônico , Ácidos Hexurônicos , Humanos , Hidrogéis , Camundongos , Camundongos SCID , Polimetil Metacrilato , Ratos
3.
PLoS One ; 19(6): e0304686, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38837998

RESUMO

Microplastics, which are tiny plastic particles less than 5 mm in diameter, are widely present in the environment, have become a serious threat to aquatic life and human health, potentially causing ecosystem disorders and health problems. The present study aimed to investigate the effects of microplastics, specifically microplastics-polystyrene (MPs-PS), on the structural integrity, gene expression related to tight junctions, and gut microbiota in mice. A total of 24 Kunming mice aged 30 days were randomly assigned into four groups: control male (CM), control female (CF), PS-exposed male (PSM), and PS-exposed female (PSF)(n = 6). There were significant differences in villus height, width, intestinal surface area, and villus height to crypt depth ratio (V/C) between the PS group and the control group(C) (p <0.05). Gene expression analysis demonstrated the downregulation of Claudin-1, Claudin-2, Claudin-15, and Occludin, in both duodenum and jejunum of the PS group (p < 0.05). Analysis of microbial species using 16S rRNA sequencing indicated decreased diversity in the PSF group, as well as reduced diversity in the PSM group at various taxonomic levels. Beta diversity analysis showed a significant difference in gut microbiota distribution between the PS-exposed and C groups (R2 = 0.113, p<0.01), with this difference being more pronounced among females exposed to MPs-PS. KEGG analysis revealed enrichment of differential microbiota mainly involved in seven signaling pathways, such as nucleotide metabolism(p<0.05). The relative abundance ratio of transcriptional pathways was significantly increased for the PSF group (p<0.01), while excretory system pathways were for PSM group(p<0.05). Overall findings suggest that MPs-PS exhibit a notable sex-dependent impact on mouse gut microbiota, with a stronger effect observed among females; reduced expression of tight junction genes may be associated with dysbiosis, particularly elevated levels of Prevotellaceae.


Assuntos
Microbioma Gastrointestinal , Microplásticos , Poliestirenos , Junções Íntimas , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Microplásticos/toxicidade , Poliestirenos/toxicidade , Camundongos , Masculino , Feminino , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , RNA Ribossômico 16S/genética , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Ocludina/metabolismo , Ocludina/genética , Claudinas/genética , Claudinas/metabolismo , Claudina-1/genética , Claudina-1/metabolismo , Proteínas de Junções Íntimas/metabolismo , Proteínas de Junções Íntimas/genética
4.
Sci Rep ; 13(1): 6393, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-37076504

RESUMO

Dentin sialophosphoprotein (DSPP) is primarily expressed by differentiated odontoblasts (dentin-forming cells), and transiently expressed by presecretory ameloblasts (enamel-forming cells). Disease-causing DSPP mutations predominantly fall into two categories: 5' mutations affecting targeting and trafficking, and 3' - 1 frameshift mutations converting the repetitive, hydrophilic, acidic C-terminal domain into a hydrophobic one. We characterized the dental phenotypes and investigated the pathological mechanisms of DsppP19L and Dspp-1fs mice that replicate the two categories of human DSPP mutations. In DsppP19L mice, dentin is less mineralized but contains dentinal tubules. Enamel mineral density is reduced. Intracellular accumulation and ER retention of DSPP is observed in odontoblasts and ameloblasts. In Dspp-1fs mice, a thin layer of reparative dentin lacking dentinal tubules is deposited. Odontoblasts show severe pathosis, including intracellular accumulation and ER retention of DSPP, strong ubiquitin and autophagy activity, ER-phagy, and sporadic apoptosis. Ultrastructurally, odontoblasts show extensive autophagic vacuoles, some of which contain fragmented ER. Enamel formation is comparable to wild type. These findings distinguish molecular mechanisms underlying the dental phenotypes of DsppP19L and Dspp-1fs mice and support the recently revised Shields classification of dentinogenesis imperfecta caused by DSPP mutations in humans. The Dspp-1fs mice may be valuable for the study of autophagy and ER-phagy.


Assuntos
Proteínas da Matriz Extracelular , Mutação da Fase de Leitura , Camundongos , Humanos , Animais , Proteínas da Matriz Extracelular/genética , Odontoblastos , Mutação , Fosfoproteínas/genética , Sialoglicoproteínas/genética , Dentina , Autofagia/genética
5.
Catheter Cardiovasc Interv ; 78(3): 413-8, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21976432

RESUMO

OBJECTIVES: We describe our experience with self-fabricated covered stents in the setting of coarctation of the aorta (CoA). BACKGROUND: Balloon-expandable covered stents are increasingly being utilized to treat CoA in older children and adults. These stents however, are not available in the United States limiting the interventionalist's ability to treat this condition safely and effectively. METHODS: Retrospective analysis and follow-up data review of our complete experience with self-fabricated covered stents for CoA. Stents were fashioned by suturing an appropriate length of tubular polytetraflouroethylene to a bare metal stent and deploying this stent across the coarctation in a standardized fashion. RESULTS: Over a 9-year period we implanted 53 balloon-expandable stents in 49 patients with CoA. Of these 13 were self-fabricated covered stents deployed in 13 patients (7 male). Median age at implantation was 25.4 years (range, 8.7-49.5 years) with median weight of 65.5 kg (range, 28-168 kg). Indications for stent placement were native coarctation/aortic atresia (n = 9), aneurysm formation (n = 3), and re-coarctation (n = 1). The median systolic pressure gradient across the coarctation of 33 mm Hg (range, 12-69 mm Hg) was reduced to 3 mm Hg (range, 0-19 mm Hg) post procedure (P < 0.001). There were no deaths on median follow-up of 44 months (range, 1-83 months). One patient developed acute contained extravasation at implantation, treated with a self-expanding stent graft. Another patient required thrombectomy for femoral arterial thrombosis. CONCLUSIONS: Innovative application of available materials adds to the armamentarium of the interventionalist. Our self-fabricated covered stent provides effective gradient reduction with no compromise in stent delivery or durability on follow-up.


Assuntos
Angioplastia com Balão/instrumentação , Coartação Aórtica/terapia , Stents , Adolescente , Adulto , Angioplastia com Balão/efeitos adversos , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/fisiopatologia , Aortografia/métodos , Pressão Sanguínea , Chicago , Criança , Feminino , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Politetrafluoretileno , Desenho de Prótese , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
6.
Gerodontology ; 28(3): 184-91, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21692833

RESUMO

OBJECTIVES: To translate the original English version of Geriatric Oral Health Assessment Index (GOHAI) into Mandarin Chinese and assess its reliability and validity for use among the elderly in inland China and to explore the factors associated with oral health-related quality of life (OHRQoL). METHODS: The original English version of GOHAI was translated, back-translated and cross-culturally adapted. The psychometric properties of GOHAI-M were assessed in a sample of 263 people aged 60 years and over and OHRQoL was examined in 221 subjects using GOHAI-M. Multiple regression analysis was conducted. RESULTS: Internal consistency of the GOHAI-M was excellent (Cronbach's α:0.81). Split-half reliability coefficient was 0.80, and item-scale correlation coefficient ranged from 0.25 to 0.71. Self-rated oral health was significantly associated with OHRQoL (r(s)=0.505, p<0.01). The relation coefficient between GOHAI-M and self-perceived need for dental treatment and number of missing teeth were 0.231 and -0.653, respectively (p<0.05). Multiple regression analysis found that better OHRQoL was significantly associated with better self-ratings of oral health (ß=0.497, p=0.01), number of missing teeth (ß=0.187, p<0.01) and life satisfaction (ß=0.132, p<0.05). CONCLUSION: The Mandarin Chinese version of GOHAI demonstrates acceptable reliability and validity. OHRQoL is associated with self-rated oral health, number of missing teeth and satisfaction with life.


Assuntos
Avaliação Geriátrica , Saúde Bucal , Qualidade de Vida , Fatores Etários , Idoso , Atitude Frente a Saúde , China , Comparação Transcultural , Assistência Odontológica , Dentaduras , Escolaridade , Feminino , Nível de Saúde , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Satisfação Pessoal , Autorrelato , Fatores Sexuais , Perda de Dente/classificação , Tradução
7.
J Biomater Appl ; 35(10): 1327-1336, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33349103

RESUMO

BACKGROUND: Laminectomy is a traditional method for treating lumbar diseases; however, the destruction of the posterior structures may cause postoperative symptoms. An individualized poly-ether-ether-ketone (PEEK) artificial lamina was designed to reconstruct the posterior structures after laminectomy. This study aimed to explore the biomechanical effects of reconstruction of the posterior structures with an individualized PEEK artificial lamina using validated finite element models. OBJECTIVE: To examine the biomechanical effects of individualized PEEK artificial lamina on postlaminectomy lumbar. METHODS: A finite element (FE) model of L3-5 was developed based on computed tomography images. Four surgical models (laminectomy, artificial lamina alone, ligament reconstruction, and osseointegration) were constructed, representing different stages of L4 artificial lamina implantation. The range of motion (ROM), intradiscal pressure (IDP), stresses in the annulus fibrosus at the surgical level and cephalad adjacent level, and stresses in the artificial lamina and screws were measured. RESULTS: The ROM, IDP, and stresses in the annulus fibrosus of the different artificial lamina models decreased compared to those of the laminectomy model at both surgical and adjacent levels for all motion patterns, most notably in the osseointegration model. In addition, the results of the stresses in the implants showed that the artificial lamina could enhance the lumbar isthmus and disperse the abnormally concentrated stresses after laminectomy. CONCLUSION: The application of a PEEK artificial lamina has the potential to stabilize the postlaminectomy lumbar spine and prevent adjacent segment disease (ASD) and iatrogenic lumbar deformities, resulting in a reduction in the incidence of post-lumbar surgery syndrome.


Assuntos
Benzofenonas/química , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Polímeros/química , Próteses e Implantes , Adulto , Anel Fibroso/fisiopatologia , Análise de Elementos Finitos , Humanos , Disco Intervertebral/fisiopatologia , Laminectomia , Masculino , Modelos Anatômicos , Parafusos Pediculares , Pressão , Amplitude de Movimento Articular , Estresse Fisiológico
8.
Int J Nanomedicine ; 16: 5755-5776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471351

RESUMO

BACKGROUND: Glioma is the most common primary malignant brain tumor with a dreadful overall survival and high mortality. One of the most difficult challenges in clinical treatment is that most drugs hardly pass through the blood-brain barrier (BBB) and achieve efficient accumulation at tumor sites. Thus, to circumvent this hurdle, developing an effectively traversing BBB drug delivery nanovehicle is of significant clinical importance. Rabies virus glycoprotein (RVG) is a derivative peptide that can specifically bind to nicotinic acetylcholine receptor (nAChR) widely overexpressed on BBB and glioma cells for the invasion of rabies virus into the brain. Inspired by this, RVG has been demonstrated to potentiate drugs across the BBB, promote the permeability, and further enhance drug tumor-specific selectivity and penetration. METHODS: Here, we used the RVG15, rescreened from the well-known RVG29, to develop a brain-targeted liposome (RVG15-Lipo) for enhanced BBB permeability and tumor-specific delivery of paclitaxel (PTX). The paclitaxel-cholesterol complex (PTX-CHO) was prepared and then actively loaded into liposomes to acquire high entrapment efficiency (EE) and fine stability. Meanwhile, physicochemical properties, in vitro and in vivo delivery efficiency and therapeutic effect were investigated thoroughly. RESULTS: The particle size and zeta potential of PTX-CHO-RVG15-Lipo were 128.15 ± 1.63 nm and -15.55 ± 0.78 mV, respectively. Compared with free PTX, PTX-CHO-RVG15-Lipo exhibited excellent targeting efficiency and safety in HBMEC and C6 cells, and better transport efficiency across the BBB in vitro model. Furthermore, PTX-CHO-RVG15-Lipo could noticeably improve the accumulation of PTX in the brain, and then promote the chemotherapeutic drugs penetration in C6luc orthotopic glioma based on in vivo imaging assays. The in vivo antitumor results indicated that PTX-CHO-RVG15-Lipo significantly inhibited glioma growth and metabasis, therefore improved survival rate of tumor-bearing mice with little adverse effect. CONCLUSION: Our study demonstrated that the RVG15 was a promising brain-targeted specific ligands owing to the superior BBB penetration and tumor targeting ability. Based on the outstanding therapeutic effect both in vitro and in vivo, PTX-CHO-RVG15-Lipo was proved to be a potential delivery system for PTX to treat glioma in clinic.


Assuntos
Neoplasias Encefálicas , Glioma , Animais , Barreira Hematoencefálica , Encéfalo , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Colesterol , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Lipossomos/uso terapêutico , Camundongos , Paclitaxel/uso terapêutico
9.
Carbohydr Polym ; 266: 118112, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34044929

RESUMO

The highly expressed P-glycoprotein (Pgp) in the intestine plays a key role in preventing drugs across the intestinal epithelium, which linked by tight junctions (TJs). Thus increasing the oral bioavailability of Pgp substrate-like drugs (PSLDs) remains a great challenge. Herein, we construct a nanocarrier system derived from Brij-grafted-chitosan (BC) to enhance the oral bioavailability and therapeutic effect of berberine (BBR, a typical PLSD) against diabetic kidney disease. The developed BC nanoparticles (BC-NPs) are demonstrated to improve the intestinal permeability of BBR via transiently and reversibly modulating the intercellular TJs (paracellular pathway) and Pgp-mediated drug efflux (transcellular pathway). As compared to free BBR and chitosan nanoparticles, the BC-NPs enhanced the relative oral bioavailability of BBR in rats (4.4- and 2.7-fold, respectively), and the therapeutic potency of BBR in renal function and histopathology. In summary, such strategy may provide an effective nanocarrier system for oral delivery of BBR and PSLDs.


Assuntos
Berberina/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Portadores de Fármacos/química , Mucosa Intestinal/metabolismo , Nanopartículas/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Berberina/química , Quitosana/química , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/patologia , Cães , Fibrose/tratamento farmacológico , Fibrose/etiologia , Fibrose/patologia , Rim/patologia , Células Madin Darby de Rim Canino , Masculino , Permeabilidade/efeitos dos fármacos , Polietilenoglicóis/química , Estudo de Prova de Conceito , Ratos Sprague-Dawley , Junções Íntimas/efeitos dos fármacos
10.
ACS Appl Mater Interfaces ; 9(48): 41767-41781, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29161013

RESUMO

Cell-penetrating peptides (CPPs), also called "Trojan-Horse" peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity ("wildness" or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent "peptide-gathering mechanical arm" (Int PMA) to curb CPPs' wildness and enhance the selectivity of R9-liposome-based cargo delivery for tumor targeting. The peptide NGR, serving as a cell-targeting peptide for anchoring, and peptide PLGLAG, serving as a substrate peptide for deanchoring, were embedded in the Int PMA motif. The Int PMA construct was designed to be sensitive to tumor microenvironmental stimuli, including aminopeptidase N (CD13) and matrix metalloproteinases (MMP-2/9). Moreover, Int PMA could be specifically recognized by tumor tissues via CD13-mediated anchoring and released for cell entry by MMP-2/9-mediated deanchoring. To test the Int PMA design, a series of experiments were conducted in vitro and in vivo. Functional conjugates Int PMA-R9-poly(ethylene glycol) (PEG)2000-distearoylphosphatidyl-ethanolamine (DSPE) and R9-PEG2000-DSPE were synthesized by Michael addition reaction and were characterized by thin-layer chromatography and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The Int PMA-R9-modified doxorubicin-loaded liposomes (Int PMA-R9-Lip-DOX) exhibited a proper particle diameter (approximately 155 nm) with in vitro sustained release characteristics. Cleavage assay showed that Int PMA-R9 peptide molecules could be cleaved by MMP-2/9 for completion of deanchoring. Flow cytometry and confocal microscopy studies indicated that Int PMA-R9-Lip-DOX can respond to both endogenous and exogenous stimuli in the presence/absence of excess MMP-2/9 and MMP-2/9 inhibitor (GM6001) and effectively function under competitive receptor-binding conditions. Moreover, Int PMA-R9-Lip-DOX generated more significant subcellular dispersions that were especially evident within endoplasmic reticulum (ER) and Golgi apparatus. Notably, Int PMA-R9-Lip-DOX could induce enhanced apoptosis, during which caspase 3/7 might be activated. In addition, Int PMA-R9-Lip-DOX displayed enhanced in vitro and in vivo antitumor efficacy versus "wild" R9-Lip-DOX. On the basis of investigations at the molecular level, cellular level, and animals' level, the control of Int PMA was effective and promoted selective delivery of R9-liposome cargo to the target site and reduced nonspecific uptake. This Int PMA-controlled strategy based on aminopeptidase-guided anchoring and protease-triggered deanchoring effectively curbed the wildness of CPPs and bolstered their effectiveness for in vivo delivery of nanotherapeutics. The specific nanocarrier delivery system used here could be adapted using a variety of intelligent designs based on combinations of multifunctional peptides that would specifically and preferentially bind to tumors versus nontumor tissues for tumor-localized accumulation in vivo. Thus, CPPs have a strong advantage for the development of intelligent nanomedicines for targeted tumor therapy.


Assuntos
Peptídeos/química , Animais , Linhagem Celular Tumoral , Peptídeos Penetradores de Células , Doxorrubicina , Sistemas de Liberação de Medicamentos , Lipossomos , Polietilenoglicóis
11.
Biomaterials ; 37: 40-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25453936

RESUMO

Cell encapsulation holds enormous potential to treat a number of hormone deficient diseases and endocrine disorders. We report a simple and universal approach to fabricate robust, hydrogel-based, nanofiber-enabled encapsulation devices (NEEDs) with macroscopic dimensions. In this design, we take advantage of the well-known capillary action that holds wetting liquid in porous media. By impregnating the highly porous electrospun nanofiber membranes of pre-made tubular or planar devices with hydrogel precursor solutions and subsequent crosslinking, we obtained various nanofiber-enabled hydrogel devices. This approach is broadly applicable and does not alter the water content or the intrinsic chemistry of the hydrogels. The devices retained the properties of both the hydrogel (e.g. the biocompatibility) and the nanofibers (e.g. the mechanical robustness). The facile mass transfer was confirmed by encapsulation and culture of different types of cells. Additional compartmentalization of the devices enabled paracrine cell co-cultures in single implantable devices. Lastly, we provided a proof-of-concept study on potential therapeutic applications of the devices by encapsulating and delivering rat pancreatic islets into chemically-induced diabetic mice. The diabetes was corrected for the duration of the experiment (8 weeks) before the implants were retrieved. The retrieved devices showed minimal fibrosis and as expected, live and functional islets were observed within the devices. This study suggests that the design concept of NEEDs may potentially help to overcome some of the challenges in the cell encapsulation field and therefore contribute to the development of cell therapies in future.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/instrumentação , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanofibras/química , Animais , Linhagem Celular Tumoral , Humanos , Transplante das Ilhotas Pancreáticas , Masculino , Fenômenos Mecânicos , Camundongos Endogâmicos C57BL , Nanofibras/ultraestrutura , Ratos Sprague-Dawley
12.
Shanghai Kou Qiang Yi Xue ; 24(2): 215-8, 2015 Apr.
Artigo em Zh | MEDLINE | ID: mdl-25938153

RESUMO

PURPOSE: To investigate the clinical efficacy of using fiber-reinforced chemical curing resin to close the inter-proximate space of the posterior teeth and block the food impaction. METHODS: One hundred and sixty-two patients with food impaction of posterior teeth were selected in this study. The total number of the food impaction was 170. They were divided into narrow-gap group and wide-gap group according to the damage of the inter-proximate space. Jingjin enamel adhesive reinforced polyethylene fiber ribbon was used in both group to close the inter-proximate space. The patients were reviewed at 6-month and 1-year. After the second follow-up examination, 161 restorations of 154 patients were included in this study. The differences between the 2 groups were analyzed by Chi-square test with SPSS 13.0 software package. RESULTS: Statistical differences were found in the retention rate of the restorations at 6-month between the 2 groups (P<0.05). The retention rate in the narrow-gap group was significantly lower than that in the wide-gap group. However, there was no significant difference between the 2 groups at 1-year. There was no significant difference in integrality between the 2 groups at 6-month and 1-year. CONCLUSIONS: The use of fiber-rein forced chemical curing resin to close the inter-proximate space of the posterior teeth and block the food impaction is more suitable for patients with clinical crown elongation, gingival recession, alveolar bone loss and the tissue damages in the inter-proximate space, which will cause food impaction.


Assuntos
Dente Pré-Molar , Restauração Dentária Permanente , Dente Molar , Resinas Sintéticas , Humanos
13.
Int J Biol Macromol ; 60: 77-82, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23707731

RESUMO

In order to improve lignin-based materials' utilization, the grafting mechanism of lignin was studied by investigating hydrogen peroxide (H2O2) initiator's effect on the structure of eucalyptus lignosulfonate calcium (HLS). HLS was treated by low content of H2O2 (H2O2/HLS(wt)=1%, 2%, 4%) under various reaction temperature and time. Changes in HLS structure were investigated by difference UV, UV, FTIR, (1)H NMR, GPC and intrinsic viscosity. The results showed that though phenolic hydroxyl group (Ph-OH) of HLS was not oxidated to the quinoid structure, its content still decreased after treated by H2O2 initiator. Meanwhile, the new aryl-alkyl ether structures and increased average molecular weight were observed. A radical coupling mechanism for the decreasing Ph-OH group's content was proposed, which radicals may terminate between phenoxy and benzyl radicals. In addition, the cleavage of methoxyl-aryl ether made a decline in the content of syringyl units, while that of guaiacyl, p-hydroxyphenyl units and free aromatic C-5 hydrogen increased when HLS reacted with H2O2.


Assuntos
Eucalyptus/química , Peróxido de Hidrogênio/química , Lignina/análogos & derivados , Lignina/química , Estrutura Molecular , Peso Molecular
14.
Arch Oral Biol ; 56(4): 367-73, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21074143

RESUMO

OBJECTIVES: The antibacterial activity and cytotoxicity of two novel cross-linking antibacterial monomers, 2-methacryloxylethyl dodecyl methyl ammonium bromide (MAE-DB) and 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB) were tested in this study. DESIGN: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of unpolymerized MAE-DB and MAE-HB against eight strains of oral bacteria were tested using a broth dilution test. Time-kill determinations were performed to examine the kinetics of unpolymerized MAE-DB and MAE-HB against Streptococcus mutans UA159 and Streptococcus sanguinis ATCC6715. Bacterial morphology was observed using a field emission scanning electron microscope (Fe-SEM). The cytotoxicity of unpolymerized two new monomers and Bis-GMA on the human gingival fibroblast cell line H2620 was assessed using a methyl thiazolyl tetrazolium assay. RESULTS: Unpolymerized MAE-DB and MAE-HB showed strong bactericidal activity against oral bacteria. The MBC value of MAE-DB ranged from 12.2 to 24.4µg/ml and the MBC value of MAE-HB ranged from 6.2 to 48.8µg/ml. Time-kill determinations indicated that unpolymerized MAE-DB and MAE-HB had rapid killing effects against S. mutans UA159 and S. sanguinis ATCC6715 at the concentration of 4× MBC. The Fe-SEM observation showed that MAE-DB and MAE-HB could disturb the integrity of bacteria and cause lysis of bacterial cells. The median lethal concentration values on human gingival fibroblast for both monomers were between 10 and 20µg/ml, and greater than that of Bis-GMA. CONCLUSIONS: Unpolymerized MAE-DB and MAE-HB monomers had strong bactericidal activity against eight strains of oral bacteria. Their cytotoxicities were less than that of Bis-GMA.


Assuntos
Antibacterianos/farmacologia , Cárie Dentária/prevenção & controle , Fibroblastos/efeitos dos fármacos , Metacrilatos/farmacologia , Doenças Periodontais/prevenção & controle , Compostos de Amônio Quaternário/farmacologia , Antibacterianos/química , Bactérias/classificação , Bactérias/efeitos dos fármacos , Células Cultivadas , Contagem de Colônia Microbiana , Cárie Dentária/microbiologia , Fibroblastos/citologia , Gengiva/citologia , Gengiva/efeitos dos fármacos , Humanos , Metacrilatos/química , Testes de Sensibilidade Microbiana , Boca/microbiologia , Doenças Periodontais/microbiologia , Polímeros , Compostos de Amônio Quaternário/química
15.
Biomaterials ; 32(11): 3042-52, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21262530

RESUMO

This work demonstrated the development of multifunctional silica nanotubes (SNT) by functionalization of their inner void and outer surface with magnetic-fluorescence nanocomposites and cationic polymers, respectively. The successful construction of BPEI-SNT was established by electron energy loss spectroscopy in conjugation with standard analytical tools. The mean fluorescence intensity in a FACS assay, a luciferase gene expression assay and a confocal fluorescence study demonstrated the efficacy of BPEI-SNT as a gene delivery vector. Endocytotic uptake was also demonstrated by the colocalization of LysoTracker Red(®) and green fluorescent quantum dots. Moreover, enhanced magnetic resonance imaging revealed the potential of the BPEI-SNT nanocomposite to act as a dual-modality nano-device.


Assuntos
Diagnóstico por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Nanotubos/química , Dióxido de Silício/química , Compostos Férricos/química , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Nanotecnologia , Nanotubos/ultraestrutura , Polietilenoimina/química , Pontos Quânticos
16.
Shanghai Kou Qiang Yi Xue ; 19(2): 129-32, 2010 Apr.
Artigo em Zh | MEDLINE | ID: mdl-20485971

RESUMO

PURPOSE: The purpose of this study was to evaluate the bleaching efficacy of non-vital discolored tooth. METHODS: Thirty-three non-vital discolored anterior teeth with intact crowns from 30 patients were included in this clinical study. Bleaching treatment was performed using a combination of intracoronal and extracoronal applications of 15% carbamide peroxide. Intracoronal bleaching with 30% hydrogen peroxide was used as control group. The effective cases of the experimental group were reexamined one year later. Statistical analysis of all data was performed with SPSS 17.0 software package. RESULTS: Combined therapy with intracoronal and extracoronal applications of 15% carbamide peroxide presented higher bleaching efficacy than intracoronal applications of 30% hydrogen peroxide alone, the difference was significant. But the color shade change one year later was not significant. CONCLUSION: A combination of intracoronal and extracoronal applications of 15% carbamide peroxide was an effective bleaching technique for non-vital discolored teeth.Supported by Key Research Project of Science and Technology Bureau of Hefei City (Grant No.2007-1016).


Assuntos
Boratos , Clareamento Dental , Idoso , Peróxido de Carbamida , Humanos , Peróxido de Hidrogênio , Peróxidos , Descoloração de Dente , Ureia/análogos & derivados
17.
ACS Nano ; 2(5): 879-88, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-19206484

RESUMO

Rare earth cerium oxide (ceria) nanoparticles are stabilized using end-functional phosphonated-PEG oligomers. The complexation process and structure of the resulting hybrid core-shell singlet nanocolloids are described, characterized, and modeled using light and neutron scattering data. The adsorption mechanism is nonstoichiometric, yielding the number of adsorbed chains per particle N(ads) = 270 at saturation. Adsorption isotherms show a high affinity of the phosphonate head for the ceria surface (adsorption energy DeltaG(ads) approximately -16kT) suggesting an electrostatic driving force for the complexation. The ease, efficiency, and integrity of the complexation is highlighted by the formation of nanometric sized cerium oxide particles covered with a well anchored PEG layer, maintaining the characteristics of the original sol. This solvating brushlike layer is sufficient to solubilize the particles and greatly expand the stability range of the original sol (

Assuntos
Cério/química , Cristalização/métodos , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia/métodos , Polietilenoglicóis/química , Coloides/química , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Pós , Solubilidade , Propriedades de Superfície , Temperatura
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