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BACKGROUND AND OBJECTIVE: The dynamic assessment of disease activity during the follow-up of patients with Crohn's disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. METHODS: In the retrospective study, patients diagnosed with CD in our hospital were included. All the diagnoses were confirmed by clinical symptoms and ileocolonoscopical results. All patients underwent intestinal ultrasound and contrast-enhanced ultrasound (CEUS) examinations within 1 week of the ileocolonoscopy examinations. Acuson Sequoia (Siemens Healthineers, Mountain View, CA, USA) and Resona R9 Elite (Mindray Medical Systems, China) with curved array and Line array transducers were used. The CEUS examination was performed with SonoVue (Bracco SpA, Milan, Italy). DCE-US analysis was performed by UltraOffice (version: 0.3-2010, Mindray Medical Systems, China) software. Two regions of interest (ROIs) were set in the anterior section of the infected bowel wall and its surrounding normal bowel wall 2 cm distant from the inflamed area. Time-intensity curves (TICs) were generated and quantitative perfusion parameters were obtained after curve fittings. The Simple Endoscopic Score for Crohn's disease (SES-CD) was regarded as the reference standard to evaluate the activity of CD. The receiver operating characteristic curve (ROC) analyses were used to determine the diagnostic efficiency of DCE-US quantitative parameters. RESULTS: From March 2023 to November 2023, 52 CD patients were included. According to SES-CD score, all patients were divided into active group with the SES-CD score > 5 (n = 39) and inactive group SES-CD score < 5 (n = 13). Most of the active CD patients showed bowel wall thickness (BWT) > 4.2 mm (97.4%, 38/39) or mesenteric fat hypertrophy (MFH) on intestinal ultrasound (US) scan (69.2%, 27/39). Color Doppler signal of the bowel wall mostly showed spotty or short striped blood flow signal in active CD patients (56.4%, 22/39). According to CEUS enhancement patterns, most active CD patients showed a complete hyperenhancement of the entire intestinal wall (61.5%, 24/39). The TICs of active CD showed an earlier enhancement, higher peak intensity, and faster decline. Among all CEUS quantitative parameters, amplitude-derived parameters peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), and wash-out rate (WoR) were significantly higher in active CD than in inactive CD (p < 0.05). The combined AUROC of intestinal ultrasound features and DCE-US quantitative perfusion parameters in the diagnosis of active CD was 0.987, with 97.4% sensitivity, 100% specificity, and 98.1% accuracy. CONCLUSIONS: DCE-US with quantitative perfusion parameters is a potential useful noninvasive imaging method to evaluate the activity of Crohn's disease.
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Given that there is no effective treatment method for lethality androgen-resistant prostate cancers (ARPC), herein we report a multifunctional gold-caged nanoparticle (PTX-PP@Au NPs) against ARPC through integrating functional organic/inorganic materials to exploit the superiors of gold particles such as photothermal effects (PTT), generating reactive oxygen species (photodynamic effects, PDT), carrying chemotherapeutic agents (chemotherapy effects, CT), and inhibiting ion channel. This synergistic PTT/PDT/CT platform consists of three components: i) the Pluronic-polyethylenimine assembling into micelles to encapsulate drugs and providing reduction sites for gold cage formation through a "green" method, ii) the gold cage with surface plasmon resonance peak at near-infrared (NIR) region in a broad window qualifying the PTT/PDT potentiality, iii) a chemotherapeutic agent paclitaxel (PTX) arresting the tumor cell cycle. As demonstrated, the system has remarkable performance on controlling drug release, blocking TRPV6 cation channel, enhancing cell cycle arrest, elevating temperature and generating ROS, thus improving cellular toxicity along with apoptosis, enhancing tumor targeting, and achieving the therapy to ARPC with low toxicity on liver function and minimal side effects to normal organs. Notably, both PTT and PDT effect are generated under single irradiation situation because of the broad absorbance window, along with limited skin damages. As a specific synergistic platform creatively integrating multiple treatment protocols with negative toxicity, PTX-PP@Au NPs provide a facile, effective, and broadly applicable strategy to deadly ARPC.
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Antineoplásicos/uso terapéutico , Oro/química , Hipertermia Inducida , Nanopartículas del Metal/química , Fotoquimioterapia , Fototerapia , Polímeros/química , Neoplasias de la Próstata/terapia , Andrógenos/uso terapéutico , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Canales de Calcio/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Endocitosis/efectos de los fármacos , Humanos , Rayos Infrarrojos , Concentración 50 Inhibidora , Masculino , Nanopartículas del Metal/ultraestructura , Ratones , Ratones Desnudos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Poloxámero/química , Polietileneimina/química , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Canales Catiónicos TRPV/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We investigated the efficacy and safety of ultrasound (US)-targeted microbubble (MB) destruction (UTMD)-enhanced delivery of monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-L-lysine (mPEG-PLGA-PLL) nanoparticles (NPs) loading Cy3-labelled platelet-derived growth factor BB (PDGF-BB) siRNA to rat retina in vivo. Eighty Wistar rats were divided into five groups (G). The right eyes, respectively, received an intravitreal injection as follows: normal saline (NS) (G1), NPs and NS (G2), NPs and MBs (G3), NPs and NS (G4) and NPs and MBs (G5). In G4 and G5, the eyes were exposed to US for 5 mins. Twenty-four hours after transfection, the uptake and distribution of Cy3-labelled siRNA in rat retina were observed by fluorescent microscope. The percentage of Cy3- labelled siRNA-positive cells was evaluated by flow cytometer. The levels of PDGF-BB mRNA in retinal pigment epithelium (RPE) cells and secreted PDGF-BB proteins were also measured. Hematoxylin and eosin staining and frozen sections were used to observe tissue damage. Our results showed that the number of Cy3-labelled siRNApositive cells in G5 was significantly higher than those of the other groups (P less than 0.05 for all comparisons). The maximum efficiency of siRNA uptake in neural retina was 18.22 +/_ 1.67%. In G4 and G5, a small number of Cy3- labelled siRNA-positive cells were also detected in the pigmented cell layer of the retina. NPs loading siRNA delivered with UTMD could more effectively down-regulate the mRNA and protein expression of PDGF-BB than NPs plus US (P=0.014 and P=0.007, respectively). Histology showed no evident tissue damage after UTMDmediated NPs loading siRNA transfection. UTMD could be used safely to enhance the delivery of mPEG-PLGAPLL NPs loading siRNA into rat retina.
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Carbocianinas/química , Ácido Láctico/química , Nanopartículas/química , Polietilenglicoles/química , Ácido Poliglicólico/química , Polilisina/química , Proteínas Proto-Oncogénicas c-sis/metabolismo , Animales , Becaplermina , Materiales Biocompatibles , Sistemas de Liberación de Medicamentos , Masculino , Microburbujas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , ARN Interferente Pequeño , Ratas , Ratas Wistar , Retina , UltrasonidoRESUMEN
A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.
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Paclitaxel Unido a Albúmina/administración & dosificación , Paclitaxel Unido a Albúmina/farmacocinética , Antineoplásicos/administración & dosificación , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Poliésteres/química , Polietilenglicoles/química , Ultrasonografía/métodos , Implantes Absorbibles , Paclitaxel Unido a Albúmina/uso terapéutico , Animales , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Medios de Contraste/síntesis química , Medios de Contraste/química , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapéutico , Humanos , Ensayo de Materiales , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Tamaño de la Partícula , Poliésteres/síntesis química , Poliésteres/farmacocinética , Polietilenglicoles/síntesis química , Polietilenglicoles/farmacocinética , Conejos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Glioblastoma (GBM) is a type of tumor that is highly lethal despite maximal therapy. Standard therapeutic approaches provide modest improvement in progression-free and overall survival, necessitating the investigation of novel therapies. Oncologic therapy has recently experienced a rapid evolution toward "targeted therapy", with drugs directed against specific targets which play essential roles in the proliferation, survival, and invasiveness of GBM cells, including numerous molecules involved in signal transduction pathways. Inhibitors of these molecules have already entered or are undergoing clinical trials. However, significant challenges in their development remain because several preclinical and clinical studies present conflicting results. In this article, we will provide an up-to-date review of the current targeted therapies in GBM.
RESUMEN
It is hypothesized that a gel (NP-Gel) composed of thermosensitive gel (Gel) and nanoparticles (NP) can prolong drug release time and overcome the drug resistance of pancreatic tumor cells. Paclitaxel (PTX)-loaded monomethoxy (polyethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine)-cyclic peptide (arginine-glycine-aspartic-glutamic-valine acid) (mPEG-PLGA-PLL-cRGD) NP and NP-Gel were designed, optimized, and characterized using dynamic light scattering, transmission electron microscopy, high efficiency liquid chromatography, and rheological analyses. Aspc-1/PTX cell was used in a cell uptake test. A 3D cell model was used to mimic PTX elimination in tissue. The in vivo sustained release and antitumor effects were studied in Aspc-1/PTX-loaded nude mice with xerographic and in situ tumors. The NP were 133.7 ± 28.3 nm with 85.03% entrapped efficiency, 1.612% loaded ratio, and suitable rheological properties. PTX was released as NP from NP-Gel, greatly prolonging the release and elimination times to afford long-term effects. NP-Gel enhanced the uptake of PTX by Aspc-1/PTX cells more than using NP or the Gel alone. Gel and NP-Gel remained solid in the tumor and stayed over 50 days versus the several days of NP in solution. NP-Gel exhibited a much higher inhibition rate in vivo than in solution, NP, or the Gel alone. In conclusion, the antitumor effects of NP-Gel might arise from synergic effects from NP and the Gel. NP primarily reversed drug resistance, while the Gel prolonged release time considerably in situ. This preparation proved effective with a very small PTX dose (250 µg/kg) and exhibited few toxic effects in normal tissue.
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Sistemas de Liberación de Medicamentos , Geles/química , Nanopartículas/química , Neoplasias Pancreáticas/tratamiento farmacológico , Poliésteres/química , Polietilenglicoles/química , Polilisina/análogos & derivados , Temperatura , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Endocitosis/efectos de los fármacos , Fluorescencia , Humanos , Ratones Desnudos , Modelos Biológicos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Polilisina/químicaRESUMEN
A combination of diagnostic and therapeutic ultrasound (US) techniques may be able to provide the basis of specific therapeutic protocols, particularly for the treatment of tumors. Nanotechnology may aid the progression towards the use of US for tumor diagnosis and targeted therapy. The current study investigated in vivo and in vitro US contrast imaging using nanocapsules (NCs), and also US and UStargeted microbubble destruction (UTMD) therapy using drugloaded NCs for pancreatic cancer in vitro. In the current study, the NCs were made from the polymer nanomaterial poly(lacticcoglycolic acid)monomethoxypoly(ethylene glycol) (PLGAmPEG), encapsulated with paclitaxel (PTX), to create PTXPLGAmPEG NCs. The PTXPLGAmPEG NCs were used as a US contrast agent (UCA), which produced satisfactory US contrastenhanced images in vitro and in vivo of the rabbit kidneys, with good contrast compared with lesions in the peripheral regions. However, clear contrastenhanced images were not obtained using PTXPLGAmPEG NCs as a UCA, when imaging the superficial pancreatic tumors of nude mice in vivo. Subsequently, fluorescence and flow cytometry were used to measure the NC uptake rate of pancreatic tumor cells under various US or UTMD conditions. An MTT assay was used to evaluate the efficiency of PTX and PTXPLGAmPEG NCs in killing tumor cells following 24 or 48 h of US or UTMD therapy, compared with controls. The specific US or UTMD conditions had been previously demonstrated to be optimal through repeated testing, to determine the conditions by which cells were not impaired and the efficiency of uptake of nanoparticles was highest. The current study demonstrated high cellular uptake rates of PLGAmPEG NCs and high tumor cell mortality with PTXPLGAmPEG NCs under US or UTMD optimal conditions. It was concluded that the use of NCs in USmediated imaging and antitumor therapy may provide a novel application for US.
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Antineoplásicos Fitogénicos/administración & dosificación , Medios de Contraste , Ácido Láctico , Microburbujas , Nanocápsulas , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Paclitaxel/administración & dosificación , Ácido Poliglicólico , Ultrasonografía/métodos , Animales , Línea Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Citometría de Flujo , Humanos , Ácido Láctico/química , Ratones , Microscopía Fluorescente , Nanocápsulas/química , Nanocápsulas/ultraestructura , Tamaño de la Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
A large number of studies have shown that bufalin can have a significant antitumor effect in a variety of tumors. However, because of toxicity, insolubility in water, fast metabolism, short half-life, and other shortcomings, its application is limited in cancer therapy. In this study, we explored the anti-metastatic role of bufalin-loaded pluronic polyetherimide nanoparticles on HCT116 colon cancer-bearing mice. Nanoparticle size, shape, drug loading, encapsulation efficiency, and in vitro drug release were studied. Also, cellular uptake of nanoparticles, in vivo tumor targeting, and tumor metastasis were studied. The nanoparticles had a particle size of about 60 nm and an encapsulation efficiency of 75.71%, by weight. The in vitro release data showed that free bufalin was released faster than bufalin-loaded pluronic polyetherimide nanoparticles, and almost 80% of free bufalin was released after 32 hours. Nanoparticles had an even size distribution, were stable, and had a slow release and a tumor-targeting effect. Bufalin-loaded pluronic polyetherimide nanoparticles can significantly inhibit the growth and metastasis of colorectal cancer.
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Antineoplásicos/química , Bufanólidos/química , Neoplasias Colorrectales/metabolismo , Nanopartículas/química , Poloxámero/química , Polímeros/química , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Bufanólidos/farmacocinética , Bufanólidos/farmacología , Neoplasias Colorrectales/patología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Células HCT116 , Humanos , Hígado/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Desnudos , Tamaño de la Partícula , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A potentially viable approach for treating late-stage prostate cancer is gene therapy. Successful gene therapy requires safe and efficient delivery systems. In this study, we report the efficient delivery of small interfering RNA (siRNA) via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. On the basis of previous findings, cyclic Arg-Gly-Asp (cRGD) peptides were conjugated to NPs to recognize the target site, integrin αvß3, expressed in high levels in PC-3 prostate cancer cells. The suppression of angiogenesis by the downregulation of vascular endothelial growth factor (VEGF) expression has been widely used to inhibit the growth of malignant tumors. In our study, human VEGF (hVEGF)-siRNA was encapsulated in NPs to inhibit VEGF expression in PC-3 cells. Concurrently, sonoporation induced by ultrasound-targeted microbubble destruction (UTMD) was utilized for the delivery of siRNA-loaded NPs. Our results showed low cytotoxicity and high gene transfection efficiency, demonstrating that the targeted delivery of biodegradable NPs with UTMD may be potentially applied as new vector system for gene delivery.
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Técnicas de Transferencia de Gen , Microburbujas , Nanopartículas/administración & dosificación , ARN Interferente Pequeño/genética , Ultrasonido/métodos , Factor A de Crecimiento Endotelial Vascular/genética , Línea Celular Tumoral , Regulación hacia Abajo , Humanos , Oligopéptidos/metabolismo , Poliésteres/metabolismo , Polietilenglicoles/metabolismo , ARN Interferente Pequeño/metabolismo , Transfección , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Small interfering RNAs (siRNAs) are valuable reagents for efficient gene silencing in a sequencespecific manner via the RNA interference (RNAi) pathway. The current synthetic siRNA structure consists of symmetrical duplexes of 1921 base pairs (bp) with 2 nucleotide (nt) 3' overhangs. In this study, we report that an asymmetric siRNA (asiRNA) consisting of 17 bp duplex region (17 bp asiRNA) exhibited potent activity in inhibiting bcl-2 gene expression and cancer cell proliferation in vitro. Importantly, this asiRNA structure significantly reduced offtarget silencing by the sense strand. To improve the stability of the 17 bp asiRNA, we synthesized a series of chemically modified 17 bp asiRNAs. Further experiments showed that in comparison with the 17 bp asiRNA, the 17 bp asiRNAM2, one of the modified 17 bp asiRNAs, exhibited a comparable gene silencing activity and an improved stability in vitro. Furthermore, the 17 bp asiRNAM2 with a proteolipid micelle delivery system can effectively suppress the growth of H22 and BGC 803 tumors in vivo. These results suggest that the chemically modified asiRNAs may have potential as an effective therapeutic approach for cancer gene therapy in the future.
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Proliferación Celular , Silenciador del Gen , Neoplasias Experimentales/prevención & control , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , ARN Interferente Pequeño/genética , Animales , Apoptosis , Citometría de Flujo , Células HeLa , Humanos , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Ratones Desnudos , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
Degradation of mRNA by RNA interference is one of the most powerful and specific mechanisms for gene silencing. However, insufficient cellular uptake and poor stability have limited its usefulness. Here, we report efficient delivery of siRNA via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. Various physicochemical properties of mPEG-PLGA-PLL NPs, including morphology, size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by scanning electron microscope, particle size and zeta potential analyzer, and high performance liquid chromatography. The levels of siRNA uptake and targeted gene inhibition were detected in human lung cancer SPC-A1-GFP cells stably expressing green fluorescent protein. Examination of the cultured SPC-A1-GFP cells with fluorescent microscope and flow cytometry showed NPs loading Cy3-labeled siRNA had much higher intracellular siRNA delivery efficiencies than siRNA alone and Lipofectamine-siRNA complexes. The gene silencing efficiency of mPEG-PLGA-PLL NPs was higher than that of commercially available transfecting agent Lipofectamine while showing no cytotoxicity. Thus, the current study demonstrates that biodegradable NPs of mPEG-PLGA-PLL triblock copolymers can be potentially applied as novel non-viral vectors for improving siRNA delivery and gene silencing.
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Materiales Biocompatibles/química , Nanopartículas/metabolismo , Polietilenglicoles/química , Poliglactina 910/química , ARN Interferente Pequeño/metabolismo , Materiales Biocompatibles/metabolismo , Materiales Biocompatibles/toxicidad , Carbocianinas/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Humanos , Lípidos/química , Microscopía Fluorescente , Nanopartículas/química , Nanopartículas/toxicidad , Tamaño de la Partícula , Poliésteres , Polietilenglicoles/metabolismo , Polietilenglicoles/toxicidad , Poliglactina 910/metabolismo , Poliglactina 910/toxicidad , Interferencia de ARN , ARN Interferente Pequeño/genética , TransfecciónRESUMEN
BACKGROUND: A novel small interfering RNA (siRNA) delivery method based on the combined use of nanoparticles (NPs) with ultrasound (US) and/or microbubbles (MBs) was introduced in the present study. We investigated the efficacy and safety of US and/or MBs-enhanced delivery of monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly l-lysine (mPEG-PLGA-PLL) NPs loading platelet-derived growth factor BB (PDGF-BB) siRNA to rat retinal pigment epithelium (RPE)-J cells. METHODS: The effect of US and/or MBs on the delivery of NPs containing Cy3-labeled siRNA was evaluated by fluorescence microscopy and flow cytometry. Potential toxicity of NPs and cell viability under different conditions of US and/or MBs were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. RESULTS: The results obtained showed that low intensity US or 15-20% MBs could increase the delivery efficiency of a lower concentration of mPEG-PLGA-PLL NPs loading siRNA to RPE-J cells, whereas the combination of US with MBs under the optimal conditions for the enhancement of NPs delivery did not further increase the cellular uptake of NPs compared to either US or MBs alone (p = 0.072 and p = 0.488, respectively). Under the optimal condition for US-enhanced NPs delivery, the enhanced PDGF-BB gene silencing with a combination of US and NPs encapsulating siRNA resulted in a significant decrease of mRNA and protein expression levels compared to NPs alone. CONCLUSIONS: US and/or MBs could be used safely to enhance the delivery of NPs loading siRNA to rat RPE-J cells. A combination of the chemical (mPEG-PLGA-PLL NPs loading siRNA) and physical (US) approaches could more effectively downregulate the mRNA and protein expression of PDGF-BB.
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Sistemas de Liberación de Medicamentos/métodos , Células Epiteliales/metabolismo , Microburbujas/uso terapéutico , Nanopartículas/administración & dosificación , Factor de Crecimiento Derivado de Plaquetas/genética , ARN Interferente Pequeño/genética , Ultrasonido , Animales , Becaplermina , Técnicas de Cultivo de Célula/métodos , Cartilla de ADN/genética , Lisina/administración & dosificación , Lisina/metabolismo , Poliésteres/administración & dosificación , Poliésteres/metabolismo , Polietilenglicoles/administración & dosificación , Polietilenglicoles/metabolismo , Proteínas Proto-Oncogénicas c-sis , Interferencia de ARN , Ratas , Epitelio Pigmentado de la Retina/citología , Epitelio Pigmentado de la Retina/metabolismoRESUMEN
Flower-like nanostructured hydroxyapatite hollow spheres (NHHS) assembled with nanosheets with a hierarchical morphology are fabricated by a rapid microwave-assisted hydrothermal route. The presence and concentration of block copolymer poly(lactide)-block-poly(ethylene glycol) (PLA-PEG) are important parameters for the formation of the hollow structure. The possible formation mechanism of NHHS is proposed. The NHHS are explored as anticancer drug carriers for cellular delivery of mitoxantrone (MIT). The MIT-loaded NHHS exhibit sustained-drug-release behavior inâ vitro and the intracellular drug-distribution tests indicate that the MIT loaded in NHHS carriers can enter the cells efficiently. The experiments also show that the NHHS have a good biocompatibility, and therefore, they are promising anticancer drug carriers in cancer chemotherapy.
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Antineoplásicos/administración & dosificación , Portadores de Fármacos/química , Durapatita/química , Mitoxantrona/administración & dosificación , Nanoestructuras/química , Animales , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular , Femenino , Humanos , Lactatos/química , Ratones , Microondas , Nanoestructuras/ultraestructura , Polietilenglicoles/químicaRESUMEN
We report room-temperature preparation of poly(ethylene glycol)-block-polylactide (PEG-PLA)/calcium phosphate (CP) nanocomposites with a porous morphology. The reaction time and concentration of the inorganic ingredients play an important role in the morphology and chemical composition of the nanocomposite. Thermogravimetry analysis shows that there is approximately 8.5 wt.% of PEG-PLA block copolymer in the nanocomposite. A typical anti-inflammatory drug, ibuprofen, is used to evaluate the drug loading ability and the release behavior of the porous PEG-PLA/CP nanocomposite. The experiments reveal that the nanocomposite has a higher drug loading capacity and favorable drug release property. The drug release kinetics of the porous PEG-PLA/CP nanocomposite is discussed as a three-stage process. The as-prepared porous PEG-PLA/CP nanocomposite is promising for application in drug delivery.
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Fosfatos de Calcio/química , Portadores de Fármacos/síntesis química , Nanocompuestos/química , Poliésteres/química , Polietilenglicoles/química , Antiinflamatorios no Esteroideos/administración & dosificación , Portadores de Fármacos/química , Ibuprofeno/administración & dosificación , Cinética , Porosidad , TemperaturaRESUMEN
Calcium phosphate (CaP) has been used as the vector for gene transfection in the past three decades with the characteristics of excellent biocompatibility and biodegradability. However, clinical application of calcium phosphate is still not popular due to poor-controlling of DNA/CaP complex preparation and its low transfection efficiency. In this study, block copolymer (PLGA-mPEG) assisted synthesis of hydroxylapatite (HAP) nanorods and DNA post-adsorbing method for transfection in vitro have been reported. By hydrothermal treatment, HAP nanorods with relatively uniform sizes of ~100 nm in length and ~25 nm in diameter and high crystallinity were prepared, which were characterized by TEM, XRD and FTIR measurements. In the presence of Ca(2+) (0.2 mol/L), HAP nanorods showed ultra-high DNA loading capacity, which was significantly enhanced by one or two magnitude compared with the recently reported high loading capacity mesoporous silica vectors. HAP nanorods, therefore, have a great potential as the gene vector to deliver DNA into the cells effectively and safely.
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ADN/química , Durapatita/química , Nanotubos/química , Polietilenglicoles/química , Poliglactina 910/química , Transfección/métodos , Adsorción , Animales , Células COS , Chlorocebus aethiops , PoliésteresRESUMEN
Plasmid(p) DNA was condensed by polycationic peptide polylysine (PLL) to be a core and then encapsulated in biodegradable monomethoxy (polyethyleneglycol)-poly(lactide-co-glycolide)-monomethoxy (poly-ethylene glycol) (PELGE) to form core-shell nanoparticles as a novel gene delivery system PPD (PELGE-PLL-DNA). Nanoparticles formed from PPD had several complementary properties such as improved biocompatibility, decreased cytotoxicity, enhanced pDNA integrity, and the characteristic of lysosomal escape as PLGA nanoparticles. The results demonstrated the potential of this PPD as an efficient gene delivery system.
Asunto(s)
ADN/administración & dosificación , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Polilisina/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Estabilidad de Medicamentos , Electroquímica , Humanos , Concentración de Iones de Hidrógeno , Ácido Láctico , Lisosomas/química , Nanopartículas , Tamaño de la Partícula , Vehículos Farmacéuticos , Plásmidos , Polietilenglicoles , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros , UltrasonidoRESUMEN
Biodegradable monomethoxy(polyethyleneglycol)-poly(lactide-co-glycolide)-monomethoxy(poly-ethyleneglycol) (PELGE) copolymers were synthesized by ring-opening polymerization to formulate plasmid DNA loaded nanoparticles. A double emulsion method with polyvinyl alcohol as the emulsifier in the external aqueous phase was employed to prepare nanoparticles. The effects of monomethoxypoly(ethyleneglycol) (mPEG) segments in the polymer on particle size, zeta potential, encapsulation efficiency and in vitro release were investigated. It was found that the introduction of a certain amount of hydrophilic mPEG segments in the copolymer chains could improve the affinity of copolymer with plasmid DNA and enhance the emulsification ability of the copolymer. Thus DNA loaded nanoparticles with smaller particle sizes and higher encapsulation efficiencies were obtained by using PELGE copolymer as the matrix.
Asunto(s)
ADN/administración & dosificación , Portadores de Fármacos/administración & dosificación , Glicolatos/administración & dosificación , Nanoestructuras , Polietilenglicoles/administración & dosificación , ADN/genética , ADN/farmacocinética , Portadores de Fármacos/farmacocinética , Glicolatos/farmacocinética , Ácido Láctico , Tamaño de la Partícula , Polietilenglicoles/farmacocinética , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
OBJECTIVE: To prepare Poly(ethylene glycol)-poly(lacticacid-co-glycolicacid)-poly(ethylene-glycol) nanoparticles (PELGE-NP) and investigate the factors affecting their diameter. METHODS: PELGE were synthesized by ring-opening polymerization, PELGE nanoparticles (PELGE-NP) were prepared by using the emulsion-solvent evaporation technique (O/W). Orthogonal design was applied to optimize the preparation technology on the basis of the single factor evaluation. RESULTS: The optimal conditions for preparing nanoparticles included the PELGE at concentration of 10 mg/ml, the ratio of acetone/DCM at 2/3, the F68 at concentration of 3%, and the volume ratio of O/W at 1/8 (V/V). CONCLUSION: The prepared PELGE nanoparticles are spherical and discrete particles without aggregation; they are smooth in surface morphology, and their diameters range from 60 nm to 100 nm.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Nanotecnología , Poliésteres/síntesis química , Poliglactina 910/síntesis química , Portadores de Fármacos , Lactatos/síntesis química , Nanotecnología/métodos , Tamaño de la Partícula , Poliésteres/química , Polietilenglicoles/síntesis química , Solventes/químicaRESUMEN
Objective. Bone-like apatite formation on the surface of calcium phosphate ceramics was believed to be the necessary step that new bone grows on the ceramics and to be relative to the osteoinductivity of the material. This study aimed at investigating the influence of the flow rate of simulated body fluid (SBF) (2 ml/min) in skeletal muscle upon the formation of bone-like apatite on porous calcium phosphate ceramics. Method. The dynamic condition was realized by controlling the SBF flowing in/out of the sample chamber of 100 ml. The flow rate of 2 ml/min is close to that in human muscle environment. The pH and inorganic ionic composition of SBF are close to those of human body fluid. Result. Bone-like apatite formation was relatively easier to occur in static SBF than in dynamic SBF. Experiment with flowing SBF (dynamic SBF) is better in mimicking the living body fluid than static SBF. Conclusion. The results from dynamic SBF may more truly show the relation between apatite layer formation and osteoinduction in biomaterials than that from in vitro experiments before.