Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Theranostics ; 9(15): 4542-4557, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285778

RESUMO

Disruption of intestine-microbiota symbiosis can result in chronic gut inflammation. We hypothesize that assessing the initial inflammatory potential of the microbiota in patients is essential and that host-derived miRNAs, which can be found in feces, could fulfill this function. We investigated whether the gut microbiota composition impacts the fecal miRNA profile and thereby indicates its ability to influence intestinal inflammation. Methods: We used high-throughput qPCR to compare fecal miRNA profile between germ-free and conventional mice. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas (IL10-/- and TLR5-/- associated microbiota) was performed. Results: We identified 12 fecal miRNAs impacted by the presence of a microbiota. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas associated with the development of intestinal inflammation (IL10-/- and TLR5-/- associated microbiota) yielded distinctively altered fecal miRNA profiles compared to that of mice receiving a "healthy" microbiota. Correlation analysis revealed the existence of interactions between the 12 abovementioned miRNAs and specific microbiota members. Conclusion: These results showed that fecal miRNA profile can be differentially and specifically impacted by microbiota composition, and that miRNA could importantly serve as markers of the colitogenic potential of the microbiota. This is particularly relevant to assess individual state of the microbiota in patients with dysbiosis-related disorders, such as IBD and potentially determine their ability to respond to therapeutics.

2.
Artigo em Inglês | MEDLINE | ID: mdl-30836147

RESUMO

The last 15 years have witnessed the emergence of a new field of research that focuses on the roles played by the intestinal microbiota in health and disease. This research field has produced accumulating evidence indicating that dysregulation of host-microbiota interactions contributes to a range of chronic inflammatory diseases, including inflammatory bowel diseases, colorectal cancer, and metabolic syndrome. Although dysregulation of the microbiota can take complex forms, in some cases, specific bacterial species that can drive specific clinical outcomes have been identified. Among the numerous factors influencing the intestinal microbiota composition, diet is a central actor, wherein numerous dietary factors can beneficially or detrimentally impact the host/microbiota relationship. This review will highlight recent literature that has advanced understanding of microbiota-diet-disease interplay, with a central focus on the following question: Are we ready to use intestinal microbiota composition-based personalized dietary interventions to treat chronic inflammatory diseases?

3.
Cancer Immunol Res ; 7(4): 544-551, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30782668

RESUMO

Gut microbiota and their metabolites are instrumental in regulating homeostasis at intestinal and extraintestinal sites. However, the complex effects of prenatal and early postnatal microbial exposure on adult health and disease outcomes remain incompletely understood. Here, we showed that mice raised under germ-free conditions until weaning and then transferred to specific pathogen-free (SPF) conditions harbored altered microbiota composition, augmented inflammatory cytokine and chemokine expression, and were hyper-susceptible to colitis-associated tumorigenesis later in adulthood. Increased number and size of colon tumors and intestinal epithelial cell proliferation in recolonized germ-free mice were associated with augmented intratumoral CXCL1, CXCL2, and CXCL5 expression and granulocytic myeloid-derived suppressor cell (G-MDSC) accumulation. Consistent with these findings, CXCR2 neutralization in recolonized germ-free mice completely reversed the exacerbated susceptibility to colitis-associated tumorigenesis. Collectively, our findings highlight a crucial role for early-life microbial exposure in establishing intestinal homeostasis that restrains colon cancer in adulthood.

4.
Sci Rep ; 8(1): 16220, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30385787

RESUMO

CD98 has been implicated in the experimental model of inflammatory bowel disease. We have previously shown that IEC-specific overexpression of CD98 mediates intestinal inflammation and intestinal epithelial barrier dysfunction. Mice overexpressing CD98 exhibited severe colitis and a greater susceptibility to CAC. Here we demonstrated CD98 overexpression to dysregulate homeostatic gradient profile of miRNA and protein expression along the ileal villus-crypt axis. Using miRNA-target gene prediction module, we observed differentially expressed miRNAs to target proteins of villus and crypt profoundly affected by CD98 overexpression. We have utilized online bioinformatics as methods to further scrutinize the biological meanings of miRNA-target data. We identified significant interactions among the differentially regulated proteins targeted by altered miRNAs in Tg mice. The biological processes affected by the predicted targets of miRNAs deviate from the homeostatic functions of the miRNA-gene-protein axis of the wildtype mice. Our results emphasize a dynamic perturbation of miRNA and protein expression in villus-crypt axis contributing to potential biological consequences of altering CD98 expression. Our findings also suggest the need for a consideration of arrays of interacting biological entities (i.e. miRNAs-mRNAs, protein-protein interaction) or a combination comparison for a better understanding of the disease pathology which is necessary for an effective therapeutic target development.

5.
Bio Protoc ; 8(9)2018 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-29951571

RESUMO

We have developed a protocol to purify RNA from DSS (Dextran Sulfate Sodium)-treated mouse tissues. This method, which prevents downstream inhibition of q-RT-PCR observed in DSS-treated tissues, relies on successive precipitations with lithium chloride.

6.
ACS Nano ; 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29860836

RESUMO

Colon cancer is among the most widely occurring cancer types, leading to considerably high mortality rate. The current chemotherapy achieves only limited success, and more effective therapeutic strategies are urgently needed. Human colonic biopsy specimens indicate increased expression of CD98 in patients with colon cancer, suggesting that CD98 might be a potential therapeutic target and/or a receptor for targeted drug delivery in colon cancer treatment. Herein, we coloaded CD98 siRNA (siCD98) and camptothecin (CPT) into CD98 Fab'-functionalized nanoparticles (NPs). The resultant Fab'-siCD98/CPT-NPs showed good monodispersity with an average diameter of approximately 270 nm and a ζ-potential of around -24 mV. These NPs mediated efficient drug delivery to the target cancer cells and tumor tissues, producing much better anticancer and antimigration effects compared to other relevant NPs. Mouse models with orthotopic colon tumors were treated with NP-embedded hydrogel, which revealed that Fab'-siCD98/CPT-NPs exhibited a therapeutic efficacy significantly better than that of single drug-loaded NPs or nonfunctionalized siCD98/CPT-NPs. This study indicates that the Fab'-siCD98/CPT-NP/hydrogel system is able to realize specific release of NPs in the colonic lumen and enable drugs (siCD98 and CPT) to be internalized into target cells, demonstrating a notable potential for clinical applications in colon-cancer-targeted combination therapy.

7.
Compr Physiol ; 8(2): 731-760, 2018 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-29687900

RESUMO

Mammalian members of the proton-coupled oligopeptide transporter family are integral membrane proteins that mediate the cellular uptake of di/tripeptides and peptide-like drugs and couple substrate translocation to the movement of H+ , with the transmembrane electrochemical proton gradient providing the driving force. Peptide transporters are responsible for the (re)absorption of dietary and/or bacterial di- and tripeptides in the intestine and kidney and maintaining homeostasis of neuropeptides in the brain. These proteins additionally contribute to absorption of a number of pharmacologically important compounds. In this overview article, we have provided updated information on the structure, function, expression, localization, and activities of PepT1 (SLC15A1), PepT2 (SLC15A2), PhT1 (SLC15A4), and PhT2 (SLC15A3). Peptide transporters, in particular, PepT1 are discussed as drug-delivery systems in addition to their implications in health and disease. Particular emphasis has been placed on the involvement of PepT1 in the physiopathology of the gastrointestinal tract, specifically, its role in inflammatory bowel diseases. © 2018 American Physiological Society. Compr Physiol 8:731-760, 2018.

8.
Gut Microbes ; : 1-4, 2018 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-29437527

RESUMO

The intestinal tract is inhabited by a large and diverse community of bacteria, collectively referred to as the gut microbiota. Composed of 500-1000 distinct species, the intestinal microbiota plays an important role in immunity and metabolism. However, alterations in its composition are associated with a variety of inflammatory diseases including obesity, diabetes, and inflammatory bowel disease (IBD). Among many other factors, our diet impacts microbiota composition and function, in either beneficial or detrimental ways. In this addendum, we will discuss our recent findings on how dietary emulsifying agents can directly and detrimentally impact the microbiota, leading to inflammatory diseases and cancer.

9.
J Biophotonics ; 11(3)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28742273

RESUMO

There remains a great need for diagnosis of inflammatory bowel disease, for which the current technique, colonoscopy, is costly and also has risks for complications. Attenuated total reflectance Fourier transform infrared spectroscopy is a new screening technique to evaluate colitis. Using second derivative spectral deconvolution of the absorbance spectra, a full set of spectral markers were identified based on statistical analysis. Using this method, Amide I group frequencies, (specifically, α-helix to ß-sheet ratio of the protein secondary structure) were identified in addition to the previously reported glucose and mannose signatures in sera of chronic and acute mice models of colitis. We also used the same technique to demonstrate that these spectral markers (α-helix/ß-sheet ratio, glucose and mannose) are recovering to basal levels upon anti-TNFα therapy. Hence, this technique will be able to identify changes in the sera due to diseases.

10.
Sci Rep ; 7(1): 2520, 2017 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-28566745

RESUMO

Inflammatory bowel disease (IBD) is difficult to diagnose due to nonspecific and variable symptoms, and lack of reliable diagnostic tests. Current methods are invasive, non-sensitive, non-predictive, and do not easily discriminate between its two main forms. Consequently, there remains a great need for reliable serum markers for IBD. Here, using a longitudinal study of various mouse models of colitis, we identified a serum miRNA signature that indicated the development of colitis and discriminated between inflammations of various origins (colitis from arthritis). Unlike the existing biomarkers, the newly identified signature also serves to distinguish individuals at risk, predict the type of inflammation, and evaluate the response to therapeutics. Moreover, the miRNA signature identified in mice predicted ulcerative colitis with 83.3% accuracy. In future, the signature identified herein could play a central role in monitoring inflammatory disorders and therapeutic responses in patients, thereby paving the way for personalized medicine.

11.
Methods Mol Biol ; 1580: 249-263, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28439838

RESUMO

Quantification of circulating microRNAs (miRNAs) is of great interest because of their potentials as disease biomarkers. Currently, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray are considered mainstream techniques for miRNA identification and quantitation. However, these techniques are challenged by the low levels and wide dynamic range (from aM to nM) of miRNAs in a physiological sample, as well as the difficulty in the implementation in point-of-care settings. Here, we describe a one-step label-free electrochemical sensing technique by assembling a triple-stem DNA-redox probe structure on a gold microelectrode and introducing a reductant, tris(2-carboxyethyl) phosphine hydrochloride (TCEP) in the detection buffer solution to achieve ultrasensitive miRNAs detection with a detection limit of 0.1 fM.


Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , MicroRNAs/análise , Animais , Sondas de DNA/química , Desenho de Equipamento , Ouro/química , Limite de Detecção , Camundongos , Microeletrodos , Oxirredução , Fosfinas/química
12.
Inflamm Bowel Dis ; 23(7): 1120-1132, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28445245

RESUMO

BACKGROUND: Lipocalin-2 (Lcn2) is a multifunctional innate immune protein that exhibits antimicrobial activity by the sequestration of bacterial siderophores, regulates iron homeostasis, and augments cellular tolerance to oxidative stress. Studies in the murine model of colitis have demonstrated that Lcn2 deficiency exacerbates colitogenesis; however, the therapeutic potential of Lcn2 supplementation has yet to be elucidated. In light of its potential mucoprotective functions, we, herein, investigated whether expression of Lcn2 in the probiotic bacterium can be exploited to alleviate experimental colitis. METHODS: Murine Lcn2 was cloned into the pT1NX plasmid and transformed into Lactococcus lactis to generate L. lactis-expressing Lcn2 (Lactis-Lcn2) or the empty plasmid (Lactis-Con). Lactis-Lcn2 was characterized by immunoblot and enzyme-linked immunosorbent assay and tested for its antimicrobial efficacy on Escherichia coli. The capacity of Lactis-Lcn2 and Lactis-Con to withstand adverse conditions was tested using in vitro viability assays. Dextran sodium sulfate colitis model was used to investigate the colonization ability and therapeutic potential of Lactis-Lcn2 and Lactis-Con. RESULTS: Lcn2 derived from Lactis-Lcn2 inhibited the growth of E. coli and reduced the bioactivity of enterobactin (E. coli-derived siderophore) in vitro. Lactis-Lcn2 displayed enhanced tolerance to adverse pH, high concentration of bile acids, and oxidative stress in vitro and survived better in the inflamed gut than Lactis-Con. Consistent with these features, Lactis-Lcn2 displayed better mucoprotection against intestinal inflammation than Lactis-Con when administered into mice with dextran sulfate sodium-induced acute colitis. CONCLUSIONS: Our findings suggest that Lcn2 expression can be exploited to enhance the survivability of probiotic bacteria during inflammation, which could further improve its efficacy to treat experimental colitis.


Assuntos
Colite/prevenção & controle , Modelos Animais de Doenças , Inflamação/prevenção & controle , Intestinos/efeitos dos fármacos , Lactococcus lactis/fisiologia , Lipocalina-2/metabolismo , Substâncias Protetoras/farmacologia , Animais , Colite/induzido quimicamente , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Expressão Ectópica do Gene , Feminino , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Lipocalina-2/genética , Camundongos , Camundongos Endogâmicos C57BL
13.
Mol Ther ; 25(7): 1628-1640, 2017 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-28143741

RESUMO

Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Portadores de Fármacos , Ácido Hialurônico/química , Hormônios Estimuladores de Melanócitos/farmacologia , Nanopartículas/química , Fragmentos de Peptídeos/farmacologia , Administração Oral , Alginatos/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Quitosana/química , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Composição de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Expressão Gênica , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Hidrogéis/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Hormônios Estimuladores de Melanócitos/química , Hormônios Estimuladores de Melanócitos/metabolismo , Camundongos , Terapia de Alvo Molecular , Nanopartículas/administração & dosagem , Tamanho da Partícula , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Células RAW 264.7 , Dodecilsulfato de Sódio , Eletricidade Estática , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
J Biophotonics ; 10(3): 465-472, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27094092

RESUMO

This article describes a rapid, simple and cost-effective technique that could lead to a screening method for colitis without the need for biopsies or in vivo measurements. This screening technique includes the testing of serum using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy for the colitis-induced increased presence of mannose. Chronic (Interleukin 10 knockout) and acute (Dextran Sodium Sulphate-induced) models for colitis are tested using the ATR-FTIR technique. Arthritis (Collagen Antibody Induced Arthritis) and metabolic syndrome (Toll like receptor 5 knockout) models are also tested as controls. The marker identified as mannose uniquely screens and distinguishes the colitic from the non-colitic samples and the controls. The reference or the baseline spectrum could be the pooled and averaged spectra of non-colitic samples or the subject's previous sample spectrum. This shows the potential of having individualized route maps of disease status, leading to personalized diagnosis and drug management.


Assuntos
Colite/diagnóstico , Colite/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Animais , Artrite Experimental/diagnóstico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Análise Química do Sangue , Colite/patologia , Colo/metabolismo , Colo/patologia , Fezes/química , Feminino , Interleucina-10/genética , Interleucina-10/metabolismo , Lipocalina-2/metabolismo , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/metabolismo
15.
Cancer Res ; 77(1): 27-40, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27821485

RESUMO

The increased risks conferred by inflammatory bowel disease (IBD) to the development of colorectal cancer gave rise to the term "colitis-associated cancer" and the concept that inflammation promotes colon tumorigenesis. A condition more common than IBD is low-grade inflammation, which correlates with altered gut microbiota composition and metabolic syndrome, both present in many cases of colorectal cancer. Recent findings suggest that low-grade inflammation in the intestine is promoted by consumption of dietary emulsifiers, a ubiquitous component of processed foods, which alter the composition of gut microbiota. Here, we demonstrate in a preclinical model of colitis-induced colorectal cancer that regular consumption of dietary emulsifiers, carboxymethylcellulose or polysorbate-80, exacerbated tumor development. Enhanced tumor development was associated with an altered microbiota metagenome characterized by elevated levels of lipopolysaccharide and flagellin. We found that emulsifier-induced alterations in the microbiome were necessary and sufficient to drive alterations in major proliferation and apoptosis signaling pathways thought to govern tumor development. Overall, our findings support the concept that perturbations in host-microbiota interactions that cause low-grade gut inflammation can promote colon carcinogenesis. Cancer Res; 77(1); 27-40. ©2016 AACR.


Assuntos
Transformação Celular Neoplásica/induzido quimicamente , Colite/induzido quimicamente , Neoplasias do Colo/induzido quimicamente , Emulsificantes/toxicidade , Aditivos Alimentares/toxicidade , Animais , Carboximetilcelulose Sódica/toxicidade , Colite/microbiologia , Neoplasias do Colo/microbiologia , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polissorbatos/toxicidade
16.
Theranostics ; 6(12): 2250-2266, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27924161

RESUMO

Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both in vitro and in vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy.


Assuntos
Anti-Inflamatórios/administração & dosagem , Produtos Biológicos/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Curcumina/administração & dosagem , Mucosa Intestinal/fisiologia , Nanopartículas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Administração Oral , Animais , Linhagem Celular , Colo/fisiologia , Portadores de Fármacos/administração & dosagem , Quimioterapia Combinada , Células Epiteliais/efeitos dos fármacos , Proteína-1 Reguladora de Fusão/antagonistas & inibidores , Ácido Hialurônico/metabolismo , Inflamação/prevenção & controle , Ácido Láctico/administração & dosagem , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Terapia de Alvo Molecular , Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Resultado do Tratamento
17.
Cancer Res ; 76(24): 7208-7218, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27742685

RESUMO

The ability of nanoparticles to target tumors and to enable site-specific drug release provides a unique system for the delivery of effective therapy with reduced toxic side effects. In this study, we used mesoporous silica nanoparticles (MSN) to fabricate a targeted drug delivery system that is responsive to hyaluronidase (HAase). Following engraftment of desthiobiotin onto the surface of MSN, a streptavidin complex was generated, which was functionalized with biotin-modified hyaluronic acid (HA) to enable controlled drug release at cancer cells expressing HAase. Various technologies were used to confirm the successful fabrication of this MSN-based nanocarrier system for targeted drug delivery. In vitro analyses showed that the release of doxorubicin hydrochloride (Dox) was accelerated significantly in the presence of biotin or HAase and accelerated further in the presence of biotin and HAase. Uptake by cancer cells was mediated efficiently by CD44 receptor-mediated endocytosis and the MSN exhibited good biocompatibility in vitro and in vivo MSN-HA/Dox nanoparticles induced apoptosis in cancer cells more efficiently than free doxorubicin and inhibited tumor growth with minimal systemic toxicity in vivo Collectively, our findings offered a preclinical proof of concept for a novel targeted drug delivery carrier system for cancer therapy. Cancer Res; 76(24); 7208-18. ©2016 AACR.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Hialuronoglucosaminidase , Nanoconjugados , Animais , Liberação Controlada de Fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Dióxido de Silício , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Mol Ther ; 24(10): 1783-1796, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27491931

RESUMO

The use of nanotechnology for drug delivery has shown great promise for improving cancer treatment. However, potential toxicity, hazardous environmental effects, issues with large-scale production, and potential excessive costs are challenges that confront their further clinical applications. Here, we describe a nanovector made from ginger-derived lipids that can serve as a delivery platform for the therapeutic agent doxorubicin (Dox) to treat colon cancer. We created nanoparticles from ginger and reassembled their lipids into ginger-derived nanovectors (GDNVs). A subsequent characterization showed that GDNVs were efficiently taken up by colon cancer cells. Viability and apoptosis assays and electric cell-substrate impedance-sensing technology revealed that GDNVs exhibited excellent biocompatibility up to 200 µmol/l; by contrast, cationic liposomes at the same concentrations decreased cell proliferation and increased apoptosis. GDNVs were capable of loading Dox with high efficiency and showed a better pH-dependent drug-release profile than commercially available liposomal-Dox. Modified GDNVs conjugated with the targeting ligand folic acid mediated targeted delivery of Dox to Colon-26 tumors in vivo and enhanced the chemotherapeutic inhibition of tumor growth compared with free drug. Current experiments explore the feasibility of producing nature-derived nanoparticles that are effective as a treatment vehicle while potentially attenuating the issues related to traditional synthetic nanoparticles.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Doxorrubicina/administração & dosagem , Gengibre/química , Lipídeos/química , Nanopartículas/química , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Células HT29 , Humanos , Camundongos , Nanopartículas/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Cell Mol Gastroenterol Hepatol ; 2(3): 340-357, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27458604

RESUMO

BACKGROUND AND AIMS: The human intestinal peptide transporter 1, hPepT1, is expressed in the small intestine at low levels in the healthy colon and upregulated during inflammatory bowel disease. hPepT1 plays a role in mouse colitis and human studies have demonstrated that chronic intestinal inflammation leads to colorectal cancer (colitis-associated cancer; CAC). Hence, we assessed here the role of PepT1 in CAC. METHODS: Mice with hPepT1 overexpression in intestinal epithelial cells (TG) or PepT1 (PepT1-KO) deletion were used and CAC was induced by AOM/DSS. RESULTS: TG mice had larger tumor sizes, increased tumor burdens, and increased intestinal inflammation compared to WT mice. Conversely, tumor number and size and intestinal inflammation were significantly decreased in PepT1-KO mice. Proliferating crypt cells were increased in TG mice and decreased in PepT1-KO mice. Analysis of human colonic biopsies revealed an increased expression of PepT1 in patients with colorectal cancer, suggesting that PepT1 might be targeted for the treatment of CAC. The use of an anti-inflammatory tripeptide KPV (Lys-Pro-Val) transported by PepT1 was able to prevent carcinogenesis in WT mice. When administered to PepT1-KO mice, KPV did not trigger any of the inhibitory effect on tumorigenesis observed in WT mice. CONCLUSIONS: The observations that pepT1 was highly expressed in human colorectal tumor and that its overexpression and deletion in mice increased and decreased colitis associated tumorigenesis, respectively, suggest that PepT1 is a potential therapeutic target for the treatment of colitis associated tumorigenesis.

20.
Tissue Barriers ; 4(2): e1134415, 2016 Apr-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27358751

RESUMO

In plant cells, nanoparticles containing miRNA, bioactive lipids and proteins serve as extracellular messengers to mediate cell-cell communication in a manner similar to the exosomes secreted by mammalian cells. Notably, such nanoparticles are edible. Moreover, given the proper origin and cargo, plant derived edible nanoparticles could function in interspecies communication and may serve as natural therapeutics against a variety of diseases. In addition, nanoparticles made of plant-derived lipids may be used to efficiently deliver specific drugs. Plant derived edible nanoparticles could be more easily scaled up for mass production, compared to synthetic nanoparticles. In this review, we discuss recent significant developments pertaining to plant derived edible nanoparticles and provide insight into the use of plants as a bio-renewable, sustainable, diversified platform for the production of therapeutic nanoparticles.


Assuntos
Nanopartículas/química , Extratos Vegetais/química , Administração Oral , Animais , Exossomos/química , Humanos , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Extratos Vegetais/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA