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1.
Carbohydr Polym ; 261: 117885, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766372

RESUMO

Rectangular V-amylose single crystals were prepared by adding racemic ibuprofen to hot dilute aqueous solutions of native and enzymatically-synthesized amylose. The lamellar thickness increased with increasing degree of polymerization of amylose and reached a plateau at about 7 nm, consistent with a chain-folding mechanism. The CP/MAS NMR spectrum as well as base-plane electron and powder X-ray diffraction patterns recorded from hydrated specimens were similar to those of V-amylose complexed with propan-2-ol. Amylose was crystallized in an orthorhombic unit cell with parameters a = 2.824 ± 0.001 nm, b = 2.966 ± 0.001 nm, and c = 0.800 ± 0.001 nm. A molecular model was proposed based on structural analogies with the Vpropan-2-ol complex and on assumptions on the stoichiometry of ibuprofen. The unit cell would contain four antiparallel 7-fold amylose single helices with ibuprofen molecules distributed inside and between the helices.


Assuntos
Amilose/química , Ibuprofeno/química , Nanopartículas/química , Varredura Diferencial de Calorimetria , Cristalização , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Estrutura Molecular , Nanoconjugados/química , Polimerização , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
2.
Molecules ; 26(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670890

RESUMO

Prostate cancer is one of the most common cancers in men. Cell invasion is an important step in the process of cancer metastasis. Herein, gold nanorods (GNRs) and polyethylene glycol (PEG)-coated GNRs were conjugated with polydopamine (PDA). The PDA-nanoconjugates demonstrated excellent colloidal stability upon lyophilization and dispersion in cell culture media with or without the addition of fetal bovine albumin (FBS), compared to unconjugated GNRs. PDA-nanoconjugates exhibited a considerable cytotoxicity against DU-145 and PC3 prostate cancer cell lines over a concentration range of 48 µg/mL-12 µg/mL, while they were biocompatible over a concentration range of 3.0 µg/mL-0.185 µg/mL. Furthermore, PDA-nanoconjugates demonstrated possible anti-invasion activity towards prostate cancer cell lines, particularly DU-145 cell line, by reducing cell migration and cell adhesion properties. The PDA-nanoconjugates could be considered a promising nano-platform toward cancer treatment by reducing the invasion activity; it could also be considered a drug delivery system for chemotherapeutic agents.


Assuntos
Antineoplásicos/química , Ouro/química , Indóis/química , Nanoconjugados/química , Nanotubos/química , Polímeros/química , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Polietilenoglicóis/química , Propriedades de Superfície
3.
Carbohydr Polym ; 255: 117490, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33436250

RESUMO

To deliver photosensitizers with PEGylated heparin (HP) into tumor cells for photodynamic therapy, we prepared two polyethylene glycol (PEG)-functionalized HP-based polymers conjugated with pyropheophorbide-a (Ppa): a non-GSH-responsive nanoagent (HP-Ppa-mPEG) with the mPEG moiety chemically attached to HP directly; and a GSH-responsive nanoagent (HP-Ppa-SS-mPEG) with the mPEG moiety conjugated to HP via a disulfide linkage. The Ppa-functionalized HP without PEGylation (HP-Ppa) was designed as another control. These amphiphilic polymers could aggregate into nanoparticles. Cellular uptake of three nanoparticles by 4T1 cells led to abundant production of reactive oxygen species after irradiation by a 660 nm laser, inducing cell apoptosis. HP-Ppa-SS-mPEG was found to achieve the highest tumor accumulation, the longest retention time and the best penetration into tumor tissues, resulting in the highest in vivo anticancer efficacy with 94.3 % tumor growth inhibition rate, suggesting that tumor microenvironment-responsive PEGylated HP-based nanomedicines may act as efficient anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Clorofila/análogos & derivados , Heparina/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/química , Feminino , Lasers , Luz , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanoconjugados/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
4.
Proc Natl Acad Sci U S A ; 117(52): 32962-32969, 2020 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-33318219

RESUMO

Clinical investigations have shown that a nonimmunogenic "cold" tumor is usually accompanied by few immunopositive cells and more immunosuppressive cells in the tumor microenvironment (TME), which is still the bottleneck of immune activation. Here, a fluorine assembly nanocluster was explored to break the shackles of immunosuppression, reawaken the immune system, and turn the cold tumor "hot." Once under laser irradiation, FS@PMPt produces sufficient reactive oxygen species (ROS) to fracture the ROS-sensitive linker, thus releasing the cisplatin conjugated PMPt to penetrate into the tumors and kill the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Meanwhile, ROS will induce potent immunogenic cell death (ICD) and further promote the accumulation of dendritic cells (DCs) and T cells, therefore not only increasing the infiltration of immunopositive cells from the outside but also reducing the immunosuppressive cells from the inside to break through the bottleneck of immune activation. The FS@PMPt nanocluster regulates the immune process in TME from negative to positive, from shallow to deep, to turn the cold tumor into a hot tumor and provoke a robust antitumor immune response.


Assuntos
Antineoplásicos/síntese química , Flúor/química , Fatores Imunológicos/síntese química , Nanoconjugados/química , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dendrímeros/química , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Fatores Imunológicos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/imunologia , Platina/química , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/imunologia
5.
Int J Mol Sci ; 21(24)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33317217

RESUMO

In this study, in vivo animal experiments with 12 nude mice bearing breast-cancer-patient-tissue-derived xenograft (PDX) tumors were performed aiming to verify the imaging capability of a novel miniaturized fluorescence molecular tomography (FMT) endoscope, in combination with targeted nanoparticle-near-infrared (NIR) dye conjugates. Tumor-bearing mice were divided into two groups by systematic injection with urokinase plasminogen activator receptor-targeted (n = 7) and nontargeted (n = 5) imaging nanoprobes as a contrast agent, respectively. Each mouse was imaged at 6, 24, and 48 h following the injection of nanoprobes using the FMT endoscope. The results show that systemic delivery of targeted nanoprobes produced a 4-fold enhancement in fluorescence signals from tumors, compared with tumors that received nontargeted nanoprobes. This study indicates that our miniaturized FMT endoscope, coupled with the targeted nanoparticle-NIR dye conjugates as a contrast agent, has high sensitivity and specificity, and thus great potential to be used for image-guided detection and removal of a primary tumor and local metastatic tumors during surgery.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Endoscópios/normas , Nanopartículas/química , Tomografia Óptica/instrumentação , Animais , Neoplasias da Mama/metabolismo , Endoscopia/instrumentação , Endoscopia/métodos , Feminino , Corantes Fluorescentes/química , Humanos , Camundongos , Camundongos Nus , Miniaturização , Nanoconjugados/química , Nanopartículas/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Tomografia Óptica/métodos , Células Tumorais Cultivadas
6.
ACS Appl Mater Interfaces ; 12(52): 57746-57756, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33325705

RESUMO

A novel concept about bifunctional antimicrobial drugs, based on self-assembling protein nanoparticles, has been evaluated here over two biofilm-forming pathogens, namely Pseudomonas aeruginosa and Staphylococcus aureus. Two structurally different antimicrobial peptides (GWH1 and PaDBS1R1) were engineered to form regular nanoparticles of around 35 nm, to which the small molecular weight drug Floxuridine was covalently conjugated. Both the assembled peptides and the chemical, a conventional cytotoxic drug used in oncotherapy, showed potent antimicrobial activities that were enhanced by the combination of both molecules in single pharmacological entities. Therefore, the resulting prototypes show promises as innovative nanomedicines, being potential alternatives to conventional antibiotics. The biological performance and easy fabrication of these materials fully support the design of protein-based hybrid constructs for combined molecular therapies, expected to have broad applicability beyond antimicrobial medicines. In addition, the approach taken here validates the functional exploration and repurposing of antitumoral drugs, which at low concentrations perform well as unexpected biofilm-inhibiting agents.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Proteínas de Fluorescência Verde/química , Nanoconjugados/química , Peptídeos Catiônicos Antimicrobianos/química , Modelos Moleculares , Conformação Proteica , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
7.
PLoS One ; 15(10): e0239814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002048

RESUMO

BACKGROUND AND STUDY AIMS: Despite major technical advancements, endoscopic surveillance for detecting premalignant lesions in Barrett's esophagus is challenging because of their flat appearance with only subtle morphological changes. Molecular endoscopic imaging (MEI) using nanoparticles (NPs), coupled with fluorescently labeled antibody permits visualization of disease-specific molecular alterations. The aim of this ex vivo study was to assess the diagnostic applicability of MEI with NPs to detect Barrett's metaplasia. PATIENTS AND METHODS: Seven patients undergoing endoscopic surveillance of known Barrett's esophagus were recruited. Freshly resected biopsy specimens were incubated with NPs coupled with FITC labeled Muc-2 antibodies and examined with MEI. Fluorescence intensity from Barrett's mucosa and control specimens were compared, followed by histological confirmation. RESULTS: Fluorescence signals, indicating the presence of goblet cells, were noted for traditional MEI using Muc-2 antibodies in Barrett's intestinal metaplasia. Significantly stronger fluorescence signals were achieved with NPs coupled with FITC-conjugated Muc-2 antibodies. The results of MEI with NPs for the prediction of Barrett's metaplasia correlated with the final histopathological examination in all the cases. CONCLUSIONS: Highly-specific NPs detected Barrett's metaplasia more efficiently than conventional MEI in this first feasibility study. MEI was as effective as standard histopathology for identifying Muc-2 containing goblet cells for diagnosis of Barrett's metaplasia. (DRKS-ID: DRKS00017747).


Assuntos
Esôfago de Barrett/diagnóstico por imagem , Endoscopia/métodos , Nanoconjugados/química , Imagem Óptica/métodos , Idoso , Anticorpos/química , Anticorpos/imunologia , Esôfago de Barrett/patologia , Fluoresceína-5-Isotiocianato/química , Humanos , Pessoa de Meia-Idade , Mucinas/imunologia
8.
Med Hypotheses ; 143: 110084, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32663741

RESUMO

COVID-19 is the pandemic outbreak that is caused by SARS-CoV-2 virus from December, 2019. Human race do not know the curative measure of this devastating disease. In today's era of nanotechnology, it may use its knowledge to develop molecular vaccine to combat this disease. In this article we are intended to propose a hypothesis on the development of a vaccine that is molecular in nature to work against COVID-19. The nanoconjugate may comprise with the inorganic nanoparticle layered double hydroxide intercalated with shRNA-plasmid that have a sequence targeting towards the viral genome or viral mRNA. This nanoconjugate may be used as a nasal spray to deliver the shRNA-plasmid to the target site. The nanoconjugate will have several advantages such as they are biocompatible, they forms as stable knockdown to the target cells and they are stable in the nasal mucosa.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/genética , Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Modelos Biológicos , Nanoconjugados/química , Plasmídeos/genética , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , RNA Interferente Pequeno/genética , RNA Viral/genética , Vacinas Sintéticas/química , Vacinas Sintéticas/genética , Vacinas Virais/síntese química
9.
Ecotoxicol Environ Saf ; 203: 110995, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32678763

RESUMO

In the present study, silver (Ag) atoms were chemically deposited on γ-alumina (Al2O3) nanospheres to be further functionalized with trithiocyanuric acid (TTC). The result was Al2O3@Ag@TTC composites, which were used for the selective extraction and preconcentration of Fe (III) and Pb (II) ions in seawater and river water samples. TTC is a potent scavenger of heavy metal ions with multiple nitrogen- and sulfur-containing functional groups. The concentrations of analytes were determined by flame atomic absorption spectrometry, and the structure of the synthetic adsorbent was characterized by spectral and microscopic techniques. Furthermore, the fundamental parameters influencing the extraction and desorption of the target ions were evaluated. Under optimized conditions, the calibration curve was linear in the range of 10-100 ng mL-1 for both analytes. The detection limits of the proposed method for Fe (III) and Pb (II) ions were 1.5 ng mL-1 and 0.8 ng mL-1, respectively, with a relative standard deviation of less than 6.1% (n = 7). Moreover, the proposed method tolerated salinities of up to 50.0 g L-1 without exhibiting any decrease in selectivity or recovery. The developed method was successfully applied to extract Fe (III) and Pb (II) ions from seawater and river water samples. The extraction recovery rates of the spiked ions were at least 93% for Fe (III) and 97 % for Pb (II).


Assuntos
Óxido de Alumínio/química , Ferro/análise , Chumbo/análise , Nanoconjugados/química , Prata/química , Triazinas/química , Poluentes Químicos da Água/análise , Água Doce/química , Concentração de Íons de Hidrogênio , Íons , Água do Mar/química , Extração em Fase Sólida/métodos
10.
J Med Chem ; 63(13): 7410-7421, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32524814

RESUMO

This paper emphasizes the synthesis of novel hybrid drug nanoparticles (Hyb-D-AuNPs) based on gold-temozolomide (TMZ) complexes combined with gemcitabine (GEM) and decitabine (DAC) to improve the efficiency and reduce the resistance of U87 malignant glial cells against TMZ. All products were evaluated by several spectroscopic techniques (Raman, UV-Vis) and transmission electron microscopy (TEM). Besides, for therapeutic purposes, the effect of these nanoparticles on cell proliferation and toxicity was evaluated, which clearly showed a synergic action of TMZ and GEM. Through the analysis of the exometabolome by nuclear magnetic resonance (NMR), the metabolic changes in the culture medium were measured in glial cells. Moreover, these nanoparticles are especially appropriated to the thermal destruction of cancer in the case of photothermal therapy due to their photothermal heating properties. This study presents an original chemical approach that it could play a central role in the field of nanomedicine, with novel perspectives for the development of new drugs and active targeting in glioblastoma multiforme (GBM) cancer therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Decitabina/farmacologia , Desoxicitidina/análogos & derivados , Glioblastoma/tratamento farmacológico , Nanoconjugados/administração & dosagem , Temozolomida/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Decitabina/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Ouro/química , Humanos , Espectroscopia de Ressonância Magnética , Nanopartículas Metálicas/química , Nanoconjugados/química , Estudo de Prova de Conceito , Espectrofotometria Ultravioleta , Temozolomida/administração & dosagem
11.
Carbohydr Polym ; 236: 116074, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32172887

RESUMO

Pluronic F-127 based dual-responsive (pH/temperature) hydrogel drug delivery system was developed involving polysaccharide-based nano-conjugate of hyaluronic acid and chitosan oligosaccharide lactate and applied for loading of gallic acid which is the principal component of traditional Chinese medicine Cortex Moutan recommended in the treatment of atopic dermatitis. The polysaccharide-based nano-conjugate was used as pH-responsive compound in the formulation and its amphiphilic character was determined colorimetrically. Microstructure analysis by SEM and TEM indicated highly porous hydrogel network and well-dispersed micellar structures, respectively, after modification with the nano-conjugate, and so, release property of the hydrogel for drug was significantly improved. Different pH-conditions were applied here to see pH-responsiveness of the formulation and increase in acidity of external environment gradually diminished mechanical stability of the hydrogel and that was reflected on the drug release property. Rheology was performed to observe sol-gel transition of the formulation and showed better rheological properties after modification with nano-conjugate. In this study, the cytotoxicity results of PF127 based formulations loaded with/without gallic acid showed cell viability of > 80.0 % for human HaCaT keratinocytes in the concentration range of 0.0-20.0 µg/ml.


Assuntos
Quitina/análogos & derivados , Ácido Hialurônico/química , Hidrogéis/química , Nanoconjugados/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quitina/química , Quitina/toxicidade , Liberação Controlada de Fármacos , Ácido Gálico/química , Humanos , Ácido Hialurônico/toxicidade , Hidrogéis/síntese química , Hidrogéis/toxicidade , Concentração de Íons de Hidrogênio , Nanoconjugados/toxicidade
12.
Pharmacol Rep ; 72(2): 368-378, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32048259

RESUMO

BACKGROUND: Ursodeoxycholic acid (UDCA) is a secondary hydrophilic bile acid, metabolised in the gut, by microbiota. UDCA is currently prescribed for primary biliary cirrhosis, and of recently has shown ß-cell protective effects, which suggests potential antidiabetic effects. Thus, this study aimed to design targeted-delivery microcapsules for oral uptake of UDCA and test its effects in type 1 diabetes (T1D). METHODS: UDCA microcapsules were produced using alginate-NM30 matrix. Three equal groups of mice (6-7 mice per group) were gavaged daily UDCA powder, empty microcapsules and UDCA microcapsules for 7 days, then T1D was induced by alloxan injection and treatments continued until mice had to be euthanised due to weight loss > 10% or severe symptoms develop. Plasma, tissues, and faeces were collected and analysed for bile acids' concentrations. RESULTS: UDCA microcapsules brought about reduction in elevated blood glucose, reduced inflammation and altered concentrations of the primary bile acid chenodeoxycholic acid and the secondary bile acid lithocholic acid, without affecting survival rate of mice. CONCLUSION: The findings suggest that UDCA exerted direct protective effects on pancreatic ß-cells and this is likely to be associated with alterations of concentrations of primary and secondary bile acids in plasma and tissues. Three equal groups of mice were gavaged daily UDCA (ursodeoxycholic acid) powder, empty microcapsules and UDCA microcapsules for 7 days, then T1D was induced and treatments continued until mice had to be euthanised. UDCA microcapsules brought about reduction in elevated blood glucose, reduced inflammation and altered concentrations of the primary bile acid chenodeoxycholic acid and the secondary bile acid lithocholic acid, without affecting survival rate of mice. The findings suggest that UDCA exerted direct protective effects on pancreatic ß-cells and this is likely to be associated with alterations of concentrations of primary and secondary bile acids in plasma and tissues.


Assuntos
Acrilatos/farmacologia , Ácidos e Sais Biliares/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nanoconjugados/química , Ácido Ursodesoxicólico/farmacologia , Acrilatos/química , Acrilatos/metabolismo , Animais , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/urina , Ácido Quenodesoxicólico/sangue , Ácido Quenodesoxicólico/metabolismo , Ácido Quenodesoxicólico/urina , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Fezes/química , Insulina/sangue , Ácido Litocólico/sangue , Ácido Litocólico/metabolismo , Ácido Litocólico/urina , Camundongos , Ácido Ursodesoxicólico/química , Ácido Ursodesoxicólico/metabolismo
13.
Int J Nanomedicine ; 15: 991-1003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103952

RESUMO

Introduction and Objective: Pancreatic cancer (PC) is characterized by a robust desmoplastic environment, which limits the uptake of the standard first-line chemotherapeutic drug gemcitabine. Enhancing gemcitabine delivery to the complex tumor microenvironment (TME) is a major clinical challenge. Molecular crosstalk between pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) plays a critical role in desmoplastic reaction in PCs. Herein, we report the development of a targeted drug delivery system to inhibit the proliferation of PCCs and PSCs in vitro. Using gold nanoparticles as the delivery vehicle, the anti-EGFR antibody cetuximab (C225/C) as a targeting agent, gemcitabine as drug and polyethylene glycol (PEG) as a stealth molecule, we created a series of targeted drug delivery systems. Methods: Fabricated nanoconjugates were characterized by various physicochemical techniques such as UV-Visible spectroscopy, transmission electron microscopy, HPLC and instrumental neutron activation analysis (INAA). Results and Conclusion: Targeted gemcitabine delivery systems containing mPEG-SH having molecular weights of 550 Da or 1000 Da demonstrated superior efficacy in reducing the viability of both PCCs and PSCs as compared to their non-targeted counterparts. EGFR-targeted pathway was further validated by pre-treating cells with C225 followed by determining cellular viability. Taken together, in our current study we have developed a PEGylated targeted nanoconjugate ACG44P1000 that showed enhanced selectivity towards pancreatic cancer cells and pancreatic stellate cells, among others, for gemcitabine delivery. We will investigate the ability of these optimized conjugates to inhibit desmoplasia and tumor growth in vivo in our future studies.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanoconjugados/química , Neoplasias Pancreáticas/tratamento farmacológico , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cetuximab/administração & dosagem , Cetuximab/química , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Portadores de Fármacos/química , Ouro/química , Humanos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Nanoconjugados/administração & dosagem , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/patologia , Polietilenoglicóis/química , Microambiente Tumoral/efeitos dos fármacos
14.
Carbohydr Polym ; 230: 115614, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887875

RESUMO

Fluorescent bioprobs are in urgent demand to monitor important biological events in biomedicine. However, the aggregation-caused quenching character, high toxicity, water-insolubility and easy leakage property of conventional small molecular dyes hinder the development in this area. In this work, an aggregation-induced emission (AIE) bioconjugate was synthesised by labeling tetraphenylethylene (TPE) to quaternized chitosan (QCS). The TPE-QCS bioconjugate emits strong fluorescence even in solid state, and is cationic and water-soluble over a wide range of pH values. The TPE-QCS aqueous solution stained HeLa cells by dose- and time-depent manner and imaged living cells with bright fluorescence. Futhermore, the cationic bioconjugate was readily internalized by cells through endocytosis, and further aggragated to large sizes and adhered to negatively charged organelle membranes inside cells achieving fluorescent cell imaging with fluorescence enhancement and leakage-free staining. The AIE-active TPE-QCS with cationic nature, good water-solubility over a wide pH range and unique cell imaging properties could trace HeLa cells for as long as 23 passages, that was obviously superior to existing commercial cellular tracer, so has promising application prospects as ultra long-term tracer in biomedical field.


Assuntos
Quitosana/análogos & derivados , Corantes Fluorescentes/química , Nanoconjugados/química , Células 3T3 , Absorção de Radiação , Animais , Cátions/química , Endocitose , Células HeLa , Humanos , Camundongos , Polimerização , Solubilidade , Estilbenos/química , Raios Ultravioleta
15.
Talanta ; 208: 120486, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816728

RESUMO

Argonaute protein (AGO2) bound circulating cell-free miRNAs (ccf-miRs), in the recent years, has attracted great attention due to their differential abundance in biological fluids. In the present work, a selective and technically uncomplicated quantum dot (QD) nanoconjugate has been fabricated combining the specific affinity of the antibody and fluorescent property of QDs for the precise immuno-detection of AGO2-bound ccf-miRs in plasma samples. The electrophoretic mobility assay confirmed the conjugation of antibody with QDs. The detection methodology involves a highly specific antigen-antibody reaction between the AGO2 proteins of miRNA-induced silencing complex and the anti-AGO2 antibody conjugated with QDs. The recognition efficiency of QD-Ab nanoconjugates was analysed using flow cytometry and fluorometry. The flow cytometry results demonstrated a significant change in the fluorescence intensity of the prepared nanoconjugates upon capture of ccf-miRs in the plasma samples with respect to the samples devoid of any miRNAs. Fluorometry measurements exhibited corroboration with the flow cytometry results indicating the selectivity and reproducibility of the developed method. Current research highlights the translational significance of the methodology as a novel flow cytometry based immunoassay for detection of differentially expressed AGO2-bound miRNAs in clinical and field settings.


Assuntos
Anticorpos/química , Proteínas Argonauta/química , MicroRNAs/sangue , Nanoconjugados/química , Pontos Quânticos/química , Anticorpos/imunologia , Proteínas Argonauta/imunologia , Imunoensaio , MicroRNAs/química
16.
Mater Sci Eng C Mater Biol Appl ; 107: 110284, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761233

RESUMO

Development of nanoparticle- and self-assembled nanomaterial-based therapeutics has become a rapidly growing area in the field of nanotechnology. One of the natural compounds, dopamine, presents as a neurotransmitter in the human brain serving as a messenger and deals with the behavioural responses, has provided an ideal platform through self-polymerization under aerobic conditions leading to the formation of a beneficial organic biopolymer, polydopamine (PDA). This polymer provides sufficient reactive functionalities, which can further be use to attach amine- or thiol-containing ligands to obtain conjugates. In the present study, self-polymerized polydopamine nanoparticles have been synthesized and tethered to aminoglycosides (AGs: Gentamicin, Kanamycin and Neomycin) through amino moieties to obtain PDA-AG nanoconjugates. These nanoconjugates are characterized by physicochemical techniques and evaluated for their antimicrobial potency against various bacterial strains including resistant ones. Simultaneously, cytocompatibility was also assessed for PDA-AG nanoconjugates. Of these three nanoconjugates (PDA-Gentamicin, PDA-Kanamycin and PDA-Neomycin), PDA-Kanamycin (PDA-K) nanoconjugate exhibited the highest activity against potent pathogens, least toxicity in human embryonic kidney (HEK 293) cells and intense toxic effects on human glioblastoma (U87) cells. Together, these results advocate the promising potential of these nanoconjugates to be used as potent antimicrobials in future applications.


Assuntos
Aminoglicosídeos , Antibacterianos , Indóis , Nanoconjugados , Polímeros , Aminoglicosídeos/química , Aminoglicosídeos/farmacologia , Aminoglicosídeos/toxicidade , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células HEK293 , Humanos , Indóis/química , Indóis/toxicidade , Testes de Sensibilidade Microbiana , Nanoconjugados/química , Nanoconjugados/toxicidade , Polímeros/química , Polímeros/toxicidade
17.
Contrast Media Mol Imaging ; 2019: 6341545, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31866799

RESUMO

Low-intensity focused ultrasound (FUS), combined with microbubbles, is able to locally, and noninvasively, open the blood-brain barrier (BBB), allowing nanoparticles to enter the brain. We present here a study on the diffusion process of gadolinium-based MRI contrast agents within the brain extracellular space after ultrasound-induced BBB permeabilization. Three compounds were tested (MultiHance, Gadovist, and Dotarem). We characterized their diffusion through in vivo experimental tests supported by theoretical models. Specifically, by estimation of the free diffusion coefficients from in vitro studies and of apparent diffusion coefficients from in vivo experiments, we have assessed tortuosity in the right striatum of 9 Sprague Dawley rats through a model correctly describing both vascular permeability as a function of time and diffusion processes occurring in the brain tissue. This model takes into account acoustic pressure, particle size, blood pharmacokinetics, and diffusion rates. Our model is able to fully predict the result of a FUS-induced BBB opening experiment at long space and time scales. Recovered values of tortuosity are in agreement with the literature and demonstrate that our improved model allows us to assess that the chosen permeabilization protocol preserves the integrity of the brain tissue.


Assuntos
Barreira Hematoencefálica/diagnóstico por imagem , Permeabilidade Capilar , Meios de Contraste/farmacocinética , Corpo Estriado/diagnóstico por imagem , Compostos Heterocíclicos/farmacocinética , Meglumina/análogos & derivados , Microbolhas , Nanoconjugados , Compostos Organometálicos/farmacocinética , Fosfolipídeos/farmacocinética , Hexafluoreto de Enxofre/farmacocinética , Ondas Ultrassônicas , Algoritmos , Animais , Barreira Hematoencefálica/efeitos da radiação , Corpo Estriado/metabolismo , Difusão , Espaço Extracelular , Masculino , Meglumina/farmacocinética , Nanoconjugados/química , Tamanho da Partícula , Imagens de Fantasmas , Ratos , Ratos Sprague-Dawley
19.
Int J Nanomedicine ; 14: 8285-8302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802866

RESUMO

Background: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate-curcumin-loaded gold-polyvinylpyrrolidone nanoparticles (FA-CurAu-PVP NPs) for targeted delivery in breast cancer model systems. Methods: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid-curcumin Au-PVP NCs (FA-CurAu-PVP NCs) were characterized by ultraviolet-visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model. Results: Curcumin (40 µg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA-CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3',5,5'-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis. Conclusion: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Ouro/química , Nanopartículas Metálicas/química , Polímeros/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/uso terapêutico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/ultraestrutura , Camundongos , Nanoconjugados/química , Povidona/química , Soro/metabolismo
20.
Int J Nanomedicine ; 14: 8483-8497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695376

RESUMO

Introduction: Controlled delivery of therapeutic molecules in a localized manner has become an area of interest due to its potential to reduce drug exposure to healthy tissues and consequently to minimize undesirable side effects. We have recently introduced novel cell-penetrating vehicles by immobilizing the antimicrobial peptide Buforin II (BUF-II) on magnetite nanoparticles (MPNPs). Despite the potent translocating abilities of such nanobioconjugates, they failed to preserve the antimicrobial activity of native BUF-II. In this work, we explored immobilization on MNPs with the aid of polymer surface spacers, which has been considered as an attractive alternative for the highly efficient conjugation of various biomolecules. Methods: Here, we immobilized BUF-II on polyetheramine-modified magnetite nanoparticles to preserve its structural integrity. As a result, for the obtained nanobioconjugates the lost antimicrobial activity against gram-positive and gram-negative bacteria was only 50% with respect to the native BUF-II. The nanobioconjugates were also characterized via FTIR, DLS, TEM, and TGA. Delivery on THP-1, HaCaT, HFF, and Escherichia coli cells was conducted to confirm capability for cell membrane translocation. Results: Colocalization with Lysotracker showed an endosomal escape efficiency of about 73∓12% in THP-1 cells. Avoidance of endocytic pathways of internalization was qualitatively confirmed by a delivery assay at low temperature. Nuclear penetration of the nanobioconjugates was corroborated via confocal microscopy and showed high biocompatibility as demonstrated by hemolysis levels below 5% and acute cytotoxicity of around 15%. Conclusion: The obtained nanobioconjugates were capable of translocating the cell membrane and nuclei of different normal and cancerous cell lines without significantly decreasing viability. This makes the vehicle addressable for a number of applications ranging from antimicrobial topical treatments to the delivery of nucleotides and therapeutic molecules with difficulties to bypass cell membranes.


Assuntos
Aminas/química , Antibacterianos/farmacologia , Peptídeos Penetradores de Células/farmacologia , Nanopartículas de Magnetita/química , Nanoconjugados/química , Proteínas/farmacologia , Antibacterianos/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/química , Endocitose/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Hemólise/efeitos dos fármacos , Humanos , Nanopartículas de Magnetita/ultraestrutura , Proteínas/química
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