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1.
J Crohns Colitis ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31710674

RESUMO

BACKGROUND AND AIMS: Epigenetic information delivered by intestinal exosomes can be useful for diagnosing intestinal diseases, such as ulcerative colitis, but the therapeutic effects of intestinal exosomes have not been fully exploited. We herein developed an autologous exosome therapy that could treat intestinal disease without any risk of inducing a systemic immunological reaction. METHODS: Intestinal exosomes were isolated and purified from feces by our newly developed multi-step sucrose gradient ultracentrifugation method. Lipopolysaccharide (LPS)-activated macrophages were employed to test the in vitro anti-inflammatory ability of intestinal exosomes. To evaluate the in vivo anti-inflammatory activity of our system, we gavaged DSS-induced colitic mice with their own healing-phase intestinal exosomes. RESULTS: Mouse intestinal exosomes are round extracellular vesicles with a hydrodynamic diameter of ~ 140 (±20) nm and a surface charge of ~ -12 (±3) mV. Among the exosomes obtained at four different stages of DSS-induced ulcerative colitis (1, before treatment; 2, DSS-treated; 3, healing-phase; and 4, back to normal), the healing-phase exosomes showed the best in vitro anti-inflammatory effects and promotion of wound healing. Moreover, oral co-administration of autologous healing-phase exosomes with DSS was found to significantly reduce the risk of a second round of DSS-induced ulcerative colitis in mice. CONCLUSIONS: Intestinal exosomes obtained during the healing phase that follows induced intestinal inflammation could strongly promote wound-healing in the host. Oral administration of autologous exosomes from the healing phase could be a safe and effective approach for treating the ulcerative colitis of a given patient in the context of personalized medicine.

3.
Nanomedicine (Lond) ; 14(17): 2373-2378, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31290366

RESUMO

The incidence of colonic diseases (e.g., inflammatory bowel diseases and colon cancer) is rapidly rising. Nanotherapeutic has been considered as a promising strategy in the treatment of colonic diseases. Silk fibroin (SF) has been widely used as a drug-carrier matrix. Interestingly, SF-based nanoparticles (SFNPs) have intrinsic anti-inflammatory activity, wound healing capacity and lysosomal environment-responsive drug-release property. With further investigations, the sequences of SF molecules could be precisely modified through chemical reactions or transgenic techniques to greatly improve the properties of SFNPs. Here, we review recent advances in the application of SFNPs toward the treatment of colonic diseases. We also discuss future developments that might improve the anti-inflammatory and anti-colon cancer activities of SF-based nanotherapeutics.

4.
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.

5.
J Crohns Colitis ; 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31168612

RESUMO

BACKGROUND AND AIMS: Heat shock protein 90 (Hsp90)-targeted therapy has been proposed as a promising strategy for the treatment of ulcerative colitis (UC) and colitis-associated cancer (CAC). The systemic administration of the Hsp90 inhibitor, 17-AAG, was found to be profoundly protective in preclinical mouse models of inflammatory bowel disease (IBD). However, the therapeutic potential of 17-AAG is limited by potential side effects associated with its systemic exposure and the modest bioavailability afforded by its oral administration. METHODS: In an effort to address these issues, we herein used a versatile single-step surface-functionalizing technique to prepare a 17-AAG oral delivery system using PLGA/PLA-PEG-FA nanoparticles (NP-PEG-FA/17-AAG). RESULTS: NP-PEG-FA could be efficiently taken up by mouse Colon-26 cells and activated Raw 264.7 cells in vitro and by inflamed mouse colitis tissues in vivo. The therapeutic efficacy of orally administrated NP-PEG-FA/17-AAG was evaluated in in vivo models using dextran sulfate sodium (DSS)-induced UC and azoxymethane (AOM)/DSS-induced CAC, and results indicated that NP-PEG-FA/17-AAG significantly alleviated the symptoms of UC and CAC. More importantly, our inflamed colitis-targeted 17-AAG nano-formulation reduced systemic exposure and provided a degree of therapeutic response similar to that obtained by systemic administration (intraperitoneal, IP) of 17-AAG, but at a 10-fold lower dose. CONCLUSIONS: We therefore describe a convenient, orally administrated 17-AAG delivery system that exhibits enhanced efficacy in UC and CAC therapy while reducing systemic exposure. This system may represent a promising therapeutic approach for treating UC and CAC.

6.
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.

7.
Mol Ther ; 27(3): 493-506, 2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30713087

RESUMO

Nanoparticles (NPs) have been utilized to deliver drugs to the intestinal epithelium in vivo. Moreover, NPs derived from edible plants are less toxic than synthetic NPs. Here, we utilized ginger NP-derived lipid vectors (GDLVs) in a proof-of-concept investigation to test the hypothesis that inhibiting expression of divalent metal-ion transporter 1 (Dmt1) would attenuate iron loading in a mouse model of hereditary hemochromatosis (HH). Initial experiments using duodenal epithelial organ cultures from intestine-specific Dmt1 knockout (KO) (Dmt1int/int) mice in the Ussing chamber established that Dmt1 is the only active iron importer during iron-deficiency anemia. Further, when Dmt1int/int mice were crossed with mice lacking the iron-regulatory hormone, hepcidin (Hepc-/-), iron loading was abolished. Hence, intestinal Dmt1 is required for the excessive iron absorption that typifies HH. Additional experiments established a protocol to produce GDLVs carrying functional Dmt1 small interfering RNAs (siRNAs) and to target these gene delivery vehicles to the duodenal epithelium in vivo (by incorporating folic acid [FA]). When FA-GDLVs carrying Dmt1 siRNA were administered to weanling Hepc-/- mice for 16 days, intestinal Dmt1 mRNA expression was attenuated and tissue iron accumulation was blunted. Oral delivery of functional siRNAs by FA-GDLVs is a suitable therapeutic approach to mitigate iron loading in murine HH.

8.
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.

9.
J Control Release ; 287: 235-246, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30107214

RESUMO

Pro-resolving factors that are critical for colonic epithelial restitution were down-regulated during the treatment with inhibitor of pro-inflammatory cytokines (e.g., anti-TNFα antibody) in ulcerative colitis (UC) therapy. We hypothesized that increased amounts of factors such as interleukin-22 (IL-22) during the therapeutic inhibition of TNFα could facilitate the resolution of intestinal inflammation. As combination therapy is an emerging strategy for UC treatment, we attempt to treat established UC based on the combination of TNFα siRNA (siTNF) and IL-22. Initially, we loaded siTNF into galactosylated polymeric nanoparticles (NPs). The resultant Gal-siTNF-NPs had a desirable average diameter (~261 nm), a narrow size distribution and a slightly negative surface charge (~-6 mV). These NPs successfully mediated the targeted delivery of siTNF to macrophages and efficiently inhibited the expression of TNFα. Meanwhile, IL-22 could obviously accelerate mucosal healing. More importantly, oral administration of Gal-siTNF-NPs plus IL-22 embedded in a hydrogel (chitosan/alginate) showed much stronger capacities to down-regulate the expression of pro-inflammatory factors and promote mucosal healing. This formulation also yielded a much better therapeutic efficacy against UC in a mouse model compared to hydrogel loaded with Gal-siTNF-NPs or IL-22 alone. Our results strongly demonstrate that Gal-siTNF-NP/IL-22-embedded hydrogel can target to inflamed colon, and co-deliver siTNF and IL-22 to boost the effects of either monotherapy, which may become a promising oral drug formulation and enable targeted combination therapy of UC.

10.
J Mater Chem B ; 6(9): 1312-1321, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30034807

RESUMO

Plant-derived edible nanoparticles (PDNPs) are nano-sized membrane vesicles released by edible plants, such as grapefruit, ginger, broccoli, and lemon. They are non-toxic, have tissue-specific targeting properties, and can be mass-produced. Thus, they have great potential for clinical application. PDNPs offer multiple advantages over the currently available drug delivery systems, such as their relatively high internalization rate, low immunogenicity, proven stability in the gastrointestinal (GI) tract, and ability to overcome the blood-brain barrier but not cross the placental barrier. In this review, we will discuss these merits of PDNPs and analyze the current issues in PDNP research.

11.
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.

12.
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.

13.
Proc Natl Acad Sci U S A ; 115(22): E5076-E5085, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29760082

RESUMO

The gut epithelium acts to separate host immune cells from unrestricted interactions with the microbiota and other environmental stimuli. In response to epithelial damage or dysfunction, immune cells are activated to produce interleukin (IL)-22, which is involved in repair and protection of barrier surfaces. However, the specific pathways leading to IL-22 and associated antimicrobial peptide (AMP) production in response to intestinal tissue damage remain incompletely understood. Here, we define a critical IL-36/IL-23/IL-22 cytokine network that is instrumental for AMP production and host defense. Using a murine model of intestinal damage and repair, we show that IL-36γ is a potent inducer of IL-23 both in vitro and in vivo. IL-36γ-induced IL-23 required Notch2-dependent (CD11b+CD103+) dendritic cells (DCs), but not Batf3-dependent (CD11b-CD103+) DCs or CSF1R-dependent macrophages. The intracellular signaling cascade linking IL-36 receptor (IL-36R) to IL-23 production by DCs involved MyD88 and the NF-κB subunits c-Rel and p50. Consistent with in vitro observations, IL-36R- and IL-36γ-deficient mice exhibited dramatically reduced IL-23, IL-22, and AMP levels, and consequently failed to recover from acute intestinal damage. Interestingly, impaired recovery of mice deficient in IL-36R or IL-36γ could be rescued by treatment with exogenous IL-23. This recovery was accompanied by a restoration of IL-22 and AMP expression in the colon. Collectively, these data define a cytokine network involving IL-36γ, IL-23, and IL-22 that is activated in response to intestinal barrier damage and involved in providing critical host defense.


Assuntos
Imunidade Inata/imunologia , Doenças Inflamatórias Intestinais/imunologia , Interleucinas/imunologia , Cicatrização/imunologia , Animais , Doenças Inflamatórias Intestinais/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Transgênicos
14.
Inflamm Bowel Dis ; 24(7): 1401-1415, 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29788186

RESUMO

10.1093/ibd/izy123_video1izy123.video15786481867001.

15.
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.

16.
J Crohns Colitis ; 12(2): 217-229, 2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-28961808

RESUMO

Background and Aims: Oral drug delivery is the most attractive pathway for ulcerative colitis [UC] therapy, since it has many advantages. However, this strategy has encountered many challenges, including the instability of drugs in the gastrointestinal tract [GT], low targeting of disease tissues, and severe adverse effects. Nanoparticles capable of colitis tissue-targeted delivery and site-specific drug release may offer a unique and therapeutically effective system that addresses these formidable challenges. Methods: We used a versatile single-step surface-functionalising technique to prepare PLGA/PLA-PEG-FA nanoparticles loaded with the ginger active compound, 6-shogaol [NPs-PEG-FA/6-shogaol]. The therapeutic efficacy of NPs-PEG-FA/6-shogaol was evaluated in the well-established mouse model of dextran sulphate sodium [DSS]-induced colitis. Results: NPs-PEG-FA exhibited very good biocompatibility both in vitro and in vivo. Subsequent cellular uptake experiments demonstrated that NPs-PEG-FA could undergo efficient receptor-mediated uptake by colon-26 cells and activated Raw 264.7 macrophage cells. In vivo, oral administration of NPs-PEG-FA/6-shogaol encapsulated in a hydrogel system [chitosan/alginate] significantly alleviated colitis symptoms and accelerated colitis wound repair in DSS-treated mice by regulating the expression levels of pro-inflammatory [TNF-α, IL-6, IL-1ß, and iNOS] and anti-inflammatory [Nrf-2 and HO-1] factors. Conclusions: Our study demonstrates a convenient, orally administered 6-shogaol drug delivery system that effectively targets colitis tissue, alleviates colitis symptoms, and accelerates colitis wound repair. This system may represent a promising therapeutic approach for treating inflammatory bowel disease [IBD].


Assuntos
Catecóis/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Nanopartículas , Cicatrização/efeitos dos fármacos , Alginatos/administração & dosagem , Animais , Materiais Biocompatíveis/administração & dosagem , Catecóis/farmacologia , Linhagem Celular , Quitosana/administração & dosagem , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Células Epiteliais/metabolismo , Ácido Fólico/administração & dosagem , Ácido Glucurônico/administração & dosagem , Heme Oxigenase-1/genética , Ácidos Hexurônicos/administração & dosagem , Hidrogéis , Interleucina-1beta/genética , Interleucina-6/genética , Mucosa Intestinal/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/genética , Camundongos , Fator 2 Relacionado a NF-E2/genética , Óxido Nítrico Sintase Tipo II/genética , Polietilenoglicóis/administração & dosagem , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética
17.
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.

18.
J Mater Chem B ; 5(29): 5881-5891, 2017 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-29081976

RESUMO

Oral drug delivery has been considered as a promising strategy for ulcerative colitis (UC) therapy. Here, an emulsion solvent evaporation technique was employed to prepare non-porous curcumin (CUR)-loaded polymeric nanoparticles (NPs) and porous CUR-loaded polymeric NPs in the absence or presence of ammonium bicarbonate. The resultant CUR-loaded NPs (non-porous NPs and porous NPs) had a desirable mean particle size of around 260 nm with a narrow size distribution, a uniform pore size distribution, slightly negative-charged surface, high encapsulation efficiency and controlled drug release capacity. In vitro experiments indicated that Raw 264.7 macrophages exhibited time-dependent accumulation profiles of NPs during the initial 2 h of co-incubation. Furthermore, we found that porous NPs inhibited the secretion of the main pro-inflammatory cytokines (TNF-α, IL-6 and IL-12) and the production of reactive oxygen species much more efficiently than non-porous NPs. Most importantly, in vivo studies demonstrated that oral administered porous NPs had a superior therapeutic efficiency in alleviating UC compared with non-porous NPs. The results collectively suggest that porous polymeric NPs can be exploited as efficient oral drug carriers for UC treatment.

19.
Nanomedicine (Lond) ; 12(16): 1927-1943, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28665164

RESUMO

AIM: To develop novel siRNA delivery system overcoming the limitations of synthetic nanoparticles, such as potential side effects, nonspecificity and economic production for ulcerative colitis therapy. MATERIALS & METHODS: Nanoparticles composed of edible ginger-derived lipid, termed ginger-derived lipid vehicles (GDLVs) were generated from ginger lipids through hydration of a lipid film, a commonly used method for a liposome fabrication. The morphology, biocompatibility and transfection efficiency of GDLVs loaded with siRNA-CD98 (siRNA-CD98/GDLVs) were characterized by standard methods. RESULTS: Orally administered siRNA-CD98/GDLVs were effectively targeted specifically to colon tissues, resulting in reduced expression of CD98. CONCLUSION: These GDLVs have great promise as efficient siRNA-delivery vehicles while potentially obviating issues related to the traditional synthetic nanoparticles. As such, they help shift the current paradigm of siRNA delivery away from artificially synthesized nanoparticles toward the use of naturally derived nanovehicles from edible plants.


Assuntos
Colite Ulcerativa/terapia , Proteína-1 Reguladora de Fusão/metabolismo , Gengibre/química , Lipídeos/química , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , Administração Oral , Animais , Apoptose , Linhagem Celular , Colo/efeitos dos fármacos , Colo/metabolismo , Portadores de Fármacos , Proteína-1 Reguladora de Fusão/genética , Terapia Genética , Humanos , Lipossomos/química , Camundongos , Tamanho da Partícula , Propriedades de Superfície , Transfecção
20.
Nanomedicine (Lond) ; 12(16): 1991-2006, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28745123

RESUMO

AIM: To enhance the tumor accumulation and targeted drug delivery for colon cancer therapy, iRGD peptide was introduced to the surface of PEGylated camptothecin-loaded nanoparticles (NPs). METHODS: Cellular uptake, targeting specificity, biodistribution and antitumor capacity were evaluated. RESULTS: The functionalization of iRGD facilitated tumor accumulation and cellular uptake of NPs by Colon-26 cells. Furthermore, the resultant iRGD-PEG-NPs remarkably improved the therapeutic efficacy of camptothecin in vitro and in vivo by inducing a higher degree of tumor cell apoptosis compared with PEG-NPs. CONCLUSION: iRGD-PEG-NP is a desired drug delivery system to facilitate the drug accumulation in orthotopic colon tumor tissues and further drug internalization by colon cancer cells.


Assuntos
Antineoplásicos/administração & dosagem , Camptotecina/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Oligopeptídeos/química , Ácido Poliglicólico/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Camptotecina/química , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Camundongos , Tamanho da Partícula , Propriedades de Superfície , Distribuição Tecidual
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