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1.
Int J Nanomedicine ; 16: 701-714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33536755

RESUMO

Atherosclerosis (AS) as the leading cause of cardiovascular and cerebrovascular events has been paid much attention all the time. With the continuous development of modern medical drug treatment, surgical treatment, interventional treatment and other methods, the mortality rate of AS has shown a downward trend, while the morbidity rate is still increasing. Oral lipid-lowering or anti-inflammatory drugs are generally used for early AS, but the relatively low accumulation efficiency in lesions and the unavoidable side effects required researchers to develop more effective drug delivery approaches for the therapy of AS. Mesoporous silica nanoparticles as nanocarrier for drug delivery have received extensive attentions due to their flexible size, high specific surface area, controlled pore volume, high drug loading capacity and excellent biocompatibility. Series of good reviews about the mesoporous silica nanoparticles loaded drugs for cancer therapy have been well documented. However, their roles as nanocarrier for drug delivery to treat AS have few reports. In this review, the applications and challenges of mesoporous silica nanomaterials in the field of the diagnosis and therapy of AS have been summarized. The classification, synthesis, formation mechanism, surface modification and functionalization of mesoporous silica nanomaterials which were closely related to the theranostic effect of AS have also been included. Last but not the least, the future prospects' suggestions of mesoporous silica nanomaterial-based drug delivery system for AS are also provided.


Assuntos
Aterosclerose/terapia , Nanoestruturas/uso terapêutico , Dióxido de Silício/uso terapêutico , Aterosclerose/diagnóstico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Porosidade
3.
Int J Nanomedicine ; 15: 6935-6944, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061360

RESUMO

Introduction: Nanoparticle solutions have been studied to improve antimicrobial effect. The aim of this study was to develop, characterize, and evaluate the in vitro and in vivo antiseptic efficacy of 0.25% aqueous-based chlorhexidine nanoemulsion (NM-Cl 0.25% w/v). Methods: The NM-Cl 0.25% w/v (2.5mg/mL) and free chlorhexidine nanoemulsion (FCN; same composition of NM-Cl without the molecule of chlorhexidine) were synthetized by the spontaneous emulsification method. Characterization analyses of physical and chemical properties were performed. The NM-Cl 0.25% w/v was compared with chlorhexidine 0.5% alcohol base (CS-Cl 0.5%) in vitro studies (microdilution study and kill curve study), and in vivo study (antisepsis of rats dorsum). Kruskal-Wallis test was used between groups and inside the same group, at different sample times and the Mann-Whitney test was performed when difference was detected. Results: The NM-Cl 0.25% w/v presented adequate physicochemical characteristics for a nanoemulsion, revealing a more basic pH than FCN and difference between zeta potential of NM-Cl 0.25% w/v and FCN. The NM-Cl 0.25% w/v and CS-Cl 0.5% solutions were more effective on Gram-positive than on Gram-negative bacteria (p≤0.05). NM-Cl 0.25% w/v presented upper antiseptic effect in the microdilution study and residual antiseptic effect was maintained for a longer time when compared to CS-Cl 0.5% (kill curve study). The four-fold (minimal inhibitory concentration) of NM-Cl 0.25% were the formulations with most durable effect within those tested, presenting residual effect until T6 for both bacteria. In the in vivo study, both formulations (NM-Cl 0.25% w/v and CS-Cl 0.5%) had a reduction of the microorganisms in the skin of the rats (p<0.0001) not revealing any difference between the formulations at different times, showing the antiseptic effect of NM-Cl (p≤0.05). Conclusion: Both in vitro and in vivo experiments demonstrated that NM-Cl showed promising future as an antiseptic for cutaneous microbiota.


Assuntos
Anti-Infecciosos Locais/farmacologia , Clorexidina/farmacologia , Emulsões/química , Nanoestruturas/química , Animais , Anti-Infecciosos Locais/química , Clorexidina/química , Emulsões/farmacologia , Etanol/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Nanoestruturas/uso terapêutico , Ratos Wistar , Pele/efeitos dos fármacos , Pele/microbiologia
4.
Cell Prolif ; 53(11): e12917, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33001510

RESUMO

OBJECTIVES: Articular cartilage plays a vital role in bearing and buffering. Injured cartilage and subchondral bone repair is a crucial challenge in cartilage tissue engineering due to the peculiar structure of osteochondral unit and the requirement of osteogenic/chondrogenic bi-directional differentiation. Based on the bionics principle, a nanotextured silk fibroin (SF)-chondroitin sulphate (CS)/hydroxyapatite (HAp) nanowire tough bilayer structure was prepared for osteochondral repair. METHODS: The SF-CS/HAp membrane was constructed by alcohol-induced ß-sheet formation serving as the physical crosslink. Its osteochondral repairing capacity was evaluated by culturing bone marrow mesenchymal stem cells (BMSCs) in vitro and constructing a rat osteochondral defect model in vivo. RESULTS: The bilayer SF-CS/HAp membrane with satisfactory mechanical properties similar to natural cartilage imitated the natural osteochondral unit structural layers and exerted the function of bearing and buffering timely after in vivo implantation. SF-CS layer upregulated the expression of chondrogenesis-related genes of BMSCs by surface nanotopography and sustained release CS. Meanwhile, nanotextured HAp layer assembled with nanowire endowed the membrane with an osteogenic differentiation tendency for BMSCs. In vivo results proved that the biomimetic bilayer structure dramatically promoted new cartilage formation and subchondral bone remodelling for osteochondral defect model after implantation. CONCLUSIONS: The SF-CS/HAp biomimetic bilayer membrane provides a promising strategy for precise osteochondral repair.


Assuntos
Durapatita/química , Fibroínas/química , Células-Tronco Mesenquimais/citologia , Nanoestruturas/química , Tecidos Suporte/química , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/uso terapêutico , Células Cultivadas , Condrogênese , Durapatita/uso terapêutico , Fibroínas/uso terapêutico , Masculino , Nanoestruturas/uso terapêutico , Nanoestruturas/ultraestrutura , Osteogênese , Ratos Sprague-Dawley
5.
Nucleic Acids Res ; 48(16): 8870-8882, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32810272

RESUMO

Extracellular vesicles (EVs) hold great promise for transporting CRISPR-Cas9 RNA-guided endonucleases (RNP) throughout the body. However, the cell-selective delivery of EVs is still a challenge. Here, we designed valency-controlled tetrahedral DNA nanostructures (TDNs) conjugated with DNA aptamer, and loaded the valency-controlled TDNs on EV surface via cholesterol anchoring for specific cell targeting. The targeting efficacy of different ratios of aptamer/cholesterol from 1:3 to 3:1 in TDNs on decorating EVs was investigated. TDNs with one aptamer and three cholesterol anchors (TDN1) efficiently facilitated the tumor-specific accumulation of the EVs in cultured HepG2 cells and human primary liver cancer-derived organoids, as well as xenograft tumor models. The intracellular delivery of RNP by TDN1-EVs successfully realized its subsequent genome editing, leading to the downregulation of GFP or WNT10B in specific cells. This system was ultimately applied to reduce the protein expression of WNT10B, which presented remarkable tumor growth inhibition in vitro, ex vivo and in vivo, and could be extended to other therapeutic targets. The present study provides a platform for the directional display of aptamer on surface labeling and the EVs-based Cas9 delivery, which provides a meaningful idea for future cell-selective gene editing.


Assuntos
Aptâmeros de Nucleotídeos/uso terapêutico , Sistemas CRISPR-Cas , Vesículas Extracelulares , Terapia Genética/métodos , Neoplasias Hepáticas/terapia , Nanoestruturas/uso terapêutico , Animais , Feminino , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Fígado/patologia , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
6.
ACS Nano ; 14(8): 9364-9388, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32667191

RESUMO

The SARS-Cov-2 pandemic has spread worldwide during 2020, setting up an uncertain start of this decade. The measures to contain infection taken by many governments have been extremely severe by imposing home lockdown and industrial production shutdown, making this the biggest crisis since the second world war. Additionally, the continuous colonization of wild natural lands may touch unknown virus reservoirs, causing the spread of epidemics. Apart from SARS-Cov-2, the recent history has seen the spread of several viral pandemics such as H2N2 and H3N3 flu, HIV, and SARS, while MERS and Ebola viruses are considered still in a prepandemic phase. Hard nanomaterials (HNMs) have been recently used as antimicrobial agents, potentially being next-generation drugs to fight viral infections. HNMs can block infection at early (disinfection, entrance inhibition) and middle (inside the host cells) stages and are also able to mitigate the immune response. This review is focused on the application of HNMs as antiviral agents. In particular, mechanisms of actions, biological outputs, and limitations for each HNM will be systematically presented and analyzed from a material chemistry point-of-view. The antiviral activity will be discussed in the context of the different pandemic viruses. We acknowledge that HNM antiviral research is still at its early stage, however, we believe that this field will rapidly blossom in the next period.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/terapia , Nanoestruturas/uso terapêutico , Pandemias , Pneumonia Viral/terapia , Imunidade Adaptativa , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Betacoronavirus/ultraestrutura , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Sistemas de Liberação de Medicamentos , Fulerenos/uso terapêutico , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Humanos , Imunidade Inata , Nanopartículas Metálicas/uso terapêutico , Modelos Biológicos , Nanotecnologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Espécies Reativas de Oxigênio/uso terapêutico , Internalização do Vírus/efeitos dos fármacos
7.
Expert Rev Med Devices ; 17(8): 751-758, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32669004

RESUMO

INTRODUCTION: aptamers are short artificial, single-strand oligonucleotide sequences (DNA, RNA or modified RNA), capable of binding to biological molecules with high affinity and specificity. Due to their relatively low cost of production and scarce immunogenicity, many efforts have been made to produce aptamers directed against specific molecular targets, such as receptors or transporters overexpressed by malignancies. AREAS COVERED: the technological approaches for generating aptamers are reviewed. Furthermore, the applications of radiolabeled aptamers for the in vivo imaging of several oncological biomarkers through single photon emission computed tomography (SPECT) or positron emission tomography (PET), are covered. Lastly, targeted therapy based on the utilization of aptamers labeled with radionuclides emitting beta particles is discussed, with particular emphasis to the oncological perspectives. EXPERT OPINION: The main limitation of radiolabeled aptamers is represented by their in vivo sensitivity to endogenous nuclease, so that several strategies have been developed to increase the stability of these compounds. Although the applications of aptamers are still in a preliminary and pre-clinical phase, it is reasonable to hypothesize that this technology will play a major role for personalized medicine in the next years.


Assuntos
Aptâmeros de Nucleotídeos/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Radioisótopos , Aptâmeros de Nucleotídeos/uso terapêutico , Humanos , Nanoestruturas/uso terapêutico , Tomografia por Emissão de Pósitrons
8.
Nat Nanotechnol ; 15(8): 646-655, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32669664

RESUMO

The COVID-19 pandemic has infected millions of people with no clear signs of abatement owing to the high prevalence, long incubation period and lack of established treatments or vaccines. Vaccines are the most promising solution to mitigate new viral strains. The genome sequence and protein structure of the 2019-novel coronavirus (nCoV or SARS-CoV-2) were made available in record time, allowing the development of inactivated or attenuated viral vaccines along with subunit vaccines for prophylaxis and treatment. Nanotechnology benefits modern vaccine design since nanomaterials are ideal for antigen delivery, as adjuvants, and as mimics of viral structures. In fact, the first vaccine candidate launched into clinical trials is an mRNA vaccine delivered via lipid nanoparticles. To eradicate pandemics, present and future, a successful vaccine platform must enable rapid discovery, scalable manufacturing and global distribution. Here, we review current approaches to COVID-19 vaccine development and highlight the role of nanotechnology and advanced manufacturing.


Assuntos
Infecções por Coronavirus/prevenção & controle , Nanoestruturas/uso terapêutico , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/uso terapêutico , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Pesquisa Biomédica/tendências , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Nanotecnologia/tendências , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Vacinas Virais/imunologia
9.
Expert Rev Anti Infect Ther ; 18(9): 849-864, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32574081

RESUMO

INTRODUCTION: The current COVID-19 pandemic caused by the SARS-CoV-2 virus demands the development of strategies not only to detect or inactivate the virus, but to treat it (therapeutically and prophylactically). COVID-19 is not only a critical threat for the population with risk factors, but also generates a dramatic economic impact in terms of morbidity and the overall interruption of economic activities. AREAS COVERED: Advanced materials are the basis of several technologies that could diminish the impact of COVID-19: biosensors might allow early virus detection, nanosized vaccines are powerful agents that could prevent viral infections, and nanosystems with antiviral activity could bind the virus for inactivation or destruction upon application of an external stimulus. Herein all these methods are discussed under the light of cutting-edge technologies and the previously reported prototypes targeting enveloped viruses similar to SARS-CoV-2. This analysis was derived from an extensive scientific literature search (including pubmed) performed on April 2020. EXPERT OPINION: Perspectives on how biosensors, vaccines, and antiviral nanosystems can be implemented to fight COVID-19 are envisioned; identifying the approaches that can be implemented in the short term and those that deserve long term research to cope with respiratory viruses-related pandemics in the future.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanoestruturas/uso terapêutico , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Técnicas Biossensoriais/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Vacinas Virais/farmacologia
10.
Int J Nanomedicine ; 15: 3181-3191, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440117

RESUMO

Objective: The aim of this concise review is to summarize the use of silver nanomaterials for caries prevention. Methods: Two researchers independently performed a literature search of publications in English using Embase, Medline, PubMed, and Scopus databases. The keywords used were (silver nanoparticles OR AgNPs OR nano silver OR nano-silver) AND (caries OR tooth decay OR remineralisation OR remineralization). They screened the title and abstract to identify potentially eligible publications. They then retrieved the full texts of the identified publications to select original research reporting silver nanomaterials for caries prevention. Results: The search identified 376 publications, and 66 articles were included in this study. The silver nanomaterials studied were categorized as resin with silver nanoparticles (n=31), silver nanoparticles (n=21), glass ionomer cement with silver nanoparticles (n=7), and nano silver fluoride (n=7). Most (59/66, 89%) studies investigated the antibacterial properties, and they all found that silver nanomaterials inhibited the adhesion and growth of cariogenic bacteria, mainly Streptococcus mutans. Although silver nanomaterials were used as anti-caries agents, only 11 (11/66, 17%) studies reported the effects of nanomaterials on the mineral content of teeth. Eight of them are laboratory studies, and they found that silver nanomaterials prevented the demineralization of enamel and dentin under an acid or cariogenic biofilm challenge. The remaining three are clinical trials that reported that silver nanomaterials prevented and arrested caries in children. Conclusion: Silver nanoparticles have been used alone or with resin, glass ionomer, or fluoride for caries prevention. Silver nanomaterials inhibit the adhesion and growth of cariogenic bacteria. They also impede the demineralization of enamel and dentin.


Assuntos
Cárie Dentária/tratamento farmacológico , Cárie Dentária/prevenção & controle , Nanoestruturas/uso terapêutico , Prata/uso terapêutico , Cariostáticos/farmacologia , Cariostáticos/uso terapêutico , Cárie Dentária/microbiologia , Esmalte Dentário/efeitos dos fármacos , Dentina/efeitos dos fármacos , Humanos , Prata/farmacologia
11.
Nanotoxicology ; 14(6): 774-787, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32401088

RESUMO

Gastric carcinoma is one of the most lethal malignant tumors. As part of our long-term efforts on seeking effective diagnosis and therapeutic strategies of gastric cancer, we present herein novel ternary copper-based chalcogenide nanoplatform CuS-NiS2 nanomaterials with outstanding photothermal (PT)/photodynamic (PD) property that could effectively suppress human gastric cancer in vitro and in vivo without obvious side effects. We revealed that CuS-NiS2 induced reactive oxygen species (ROS) generation, leading to apoptosis through Bcl-2/Bax pathway of human gastric cancer cells under 808 nm near-infrared (NIR) irradiation. In addition, we also confirmed that the combination of CuS-NiS2 and 808 nm NIR laser treatment triggered necroptosis by regulating the novel pathway MLKL/CAPG of human gastric cancer cells. Moreover, the CuS-NiS2 exhibited excellent contrast enhancement according to magnetic resonance imaging (MRI). Taken together, we reported new ternary copper-based chalcogenide nanomaterials CuS-NiS2, which could be successfully applied for MRI-guided PT/PD therapy of gastric carcinoma through mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.


Assuntos
Apoptose/efeitos dos fármacos , Cobre/uso terapêutico , Proteínas dos Microfilamentos/metabolismo , Mitocôndrias/efeitos dos fármacos , Nanoestruturas/uso terapêutico , Necroptose/efeitos dos fármacos , Níquel/uso terapêutico , Proteínas Nucleares/metabolismo , Fototerapia/métodos , Proteínas Quinases/metabolismo , Neoplasias Gástricas/terapia , Animais , Linhagem Celular Tumoral , Cobre/administração & dosagem , Humanos , Imagem por Ressonância Magnética , Masculino , Camundongos Nus , Mitocôndrias/metabolismo , Nanoestruturas/administração & dosagem , Níquel/administração & dosagem , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Int J Nanomedicine ; 15: 1967-1981, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273697

RESUMO

Purpose: To synthesize and evaluate a novel folate-conjugated ultrasonic nanobubble (HA-FOL-NB) loading low-molecular-weight hyaluronic acid (LMW-HA) for specific tumor-associated macrophages (TAMs) targeting and reeducation. Methods: The characteristics, cytotoxicity, contrast-enhanced ultrasound imaging (CEUS), and targeting ability to TAMs of HA-FOL-NBs were investigated. The TAMs reprogramming function of HA-FOL-NBs combining ultrasound targeted nanobubble destruction was assessed as well. Results: HA-FOL-NBs (about 342 nm) showed remarkable contrast enhancement images, and higher targeting ability due to the folate to folate receptor interactions. Combined with ultrasound targeted nanobubble destruction, HA-FOL-NBs could specifically deliver LMW-HA into TAMs, thus exhibited stronger reeducation effect compared with free LMW-HA. Conclusion: These folate-conjugated and LMW-HA-loaded nanobubbles, with targeted CEUS imaging and TAMs reeducation, are expected to be a potential approach for tumor therapy based on TAMs, especially folate receptor-positive ones.


Assuntos
Ácido Fólico/química , Ácido Hialurônico/farmacologia , Macrófagos/efeitos dos fármacos , Nanoestruturas/administração & dosagem , Ultrassonografia de Intervenção/métodos , Animais , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/patologia , Sistemas de Liberação de Medicamentos/métodos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Macrófagos/patologia , Camundongos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Células RAW 264.7
14.
Int J Nanomedicine ; 15: 2045-2058, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273701

RESUMO

Bone regeneration remains a great clinical challenge. Two-dimensional materials, especially graphene and its derivative graphene oxide, have been widely used for bone regeneration. Since its discovery in 2014, black phosphorus (BP) nanomaterials including BP nanosheets and BP quantum dots have attracted considerable scientific attention and are considered as prospective graphene substitutes. BP nanomaterials exhibit numerous advantages such as excellent optical and mechanical properties, electrical conductivity, excellent biocompatibility, and good biodegradation, all of which make them particularly attractive in biomedicine. In this review, we comprehensively summarize recent advances of BP-based nanomaterials in bone regeneration. The advantages are reviewed, the different synthesis methods of BP are summarized, and the applications to promote bone regeneration are highlighted. Finally, the existing challenges and perspectives of BP in bone regeneration are briefly discussed.


Assuntos
Regeneração Óssea/fisiologia , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Fósforo/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Grafite/química , Humanos , Pontos Quânticos/química
15.
Nanoscale Horiz ; 5(3): 400-430, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32118219

RESUMO

Photothermal therapy (PTT) is one of the most promising techniques for cancer tumor ablation. Nanoparticles are increasingly being investigated for use with PTT and can serve as theranostic agents. Based on the ability of near-infrared nano-photo-absorbers to generate heat under laser irradiation, PTT could prove advantageous in certain situations over more classical cancer therapies. To analyze the efficacy of nanoparticle-based PTT, preclinical in vitro studies typically use 2D cultures, but this method cannot completely mimic the complex tumor organization, bioactivity, and physiology that all control the complex penetration depth, biodistribution, and tissue diffusion parameters of nanomaterials in vivo. To fill this knowledge gap, 3D culture systems have been explored for PTT analysis. These models provide more realistic microenvironments that allow spatiotemporal oxygen gradients and cancer cell adaptations to be considered. This review highlights the work that has been done to advance 3D models for cancer microenvironment modeling, specifically in the context of advanced, functionalized nanoparticle-directed PTT.


Assuntos
Técnicas de Cultura de Células/métodos , Hipertermia Induzida/métodos , Nanoestruturas/uso terapêutico , Fototerapia/métodos , Linhagem Celular Tumoral , Humanos , Raios Infravermelhos/uso terapêutico , Lasers , Esferoides Celulares , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
16.
Cell Prolif ; 53(4): e12787, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32162733

RESUMO

OBJECTIVES: To provide a new research direction for nerve regeneration and strategy for Alzheimer's disease treatment, tetrahedral DNA nanostructures (TDNs)-novel tetrahedral framework nucleic acid molecule nanoparticles (tFNA) that can inhibit the apoptosis of nerve cells are employed in the experiment. MATERIALS AND METHODS: To verify the successful preparation of TDNs, the morphology of TDNs was observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM). The expression of apoptosis-related genes and proteins was investigated by confocal microscope, flow cytometry, PCR and Western blot to detect the impact of TDNs on the Alzheimer's model. And finally, Morris water maze experiment was used to test behavioural changes and Nissl stain was detected to observe the morphology and quantity of neurons in the hippocampus. Immunofluorescence stain was used to observe the Aß stain, and TUNEL dyeing was utilized to observe neuronal apoptosis. RESULTS: In vitro and in vivo experiments confirm that TDNs, in a specific concentration range, have no toxic or side effects on nerve cells, can effectively inhibit apoptosis in an Alzheimer's disease cell model and effectively improve memory and learning ability in a rat model of Alzheimer's disease. CONCLUSIONS: These findings suggest that TDNs may be a promising drug for the treatment of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , DNA/uso terapêutico , Nanoestruturas/uso terapêutico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Animais , Apoptose/efeitos dos fármacos , DNA/farmacocinética , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Modelos Moleculares , Nanoestruturas/ultraestrutura , Células PC12 , Ratos , Ratos Sprague-Dawley
17.
J Photochem Photobiol B ; 204: 111808, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32006892

RESUMO

Photodynamic therapy (PDT) is effective in the treatment of different types of cancer, such as basal cell carcinoma and other superficial cancers. However, improvements in photosensitizer delivery are still needed, and the use of PDT against more deeply located tumors has been the subject of many studies. Thus, the goal of this study was to evaluate the efficacy of a nanoemulsion containing aluminium-phthalocyanine (AlPc-NE) as a mediator of photodynamic therapy (PDT-AlPc-NE) against grafted 4T1 breast adenocarcinoma tumors in mice (BALB/c). Short after the appearance of the tumor, the animals were divided into groups (n = 5) as follows: untreated; only AlPc-NE and treated with PDT-AlPc-NE. The tumor volume was measured with a digital calliper at specific times. The presence of metastasis in the lungs was evaluated by microtomography and histopathological analyses. The results show that the application of PDT-AlPc-NE eradicated the transplanted tumors in all the treated animals, while the animals from control groups presented a robust increase in the tumor volume. Still more significantly, microtomography showed the animals submitted the PDT-AlPc-NE to be free of detectable metastasis in the lungs. The histological analysis of the lungs further confirmed the results verified by the microtomography. Therefore, this study suggests that PDT-AlPc-NE is effective in the elimination of experimentally grafted breast tumors in mice and also in preventing the formation of metastasis in the lungs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Alumínio/química , Neoplasias da Mama/tratamento farmacológico , Indóis/química , Neoplasias Pulmonares/tratamento farmacológico , Nanoestruturas/química , Fármacos Fotossensibilizantes/uso terapêutico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/uso terapêutico , Nanoestruturas/toxicidade , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Transplante Homólogo , Microtomografia por Raio-X
18.
Life Sci ; 245: 117394, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32017870

RESUMO

Neurodegenerative diseases need the drugs to be delivered right inside the brain to maximizing the therapeutic effects. This can be achieved by use of novel targeted delivery systems such as nanoemulsions. Nanoemulsions (NE) are nano-sized emulsions that are manufactured for enhancing the delivery of drugs to the targeted site and minimize adverse effects and toxic reactions. Looking into the advanced pharmaceutical applications of NE, the present review gives an insight to the understanding of the application of NE in NDs like AD, PD and Prion's disease. The review also touches upon the pathophysiology of these ND diseases to have a clear understanding of the molecular aspects of the disease. Finally, the review sets a standpoint of nanoemulsion's significance in the treatment therapy of ND besides the drawbacks associated with the current drug therapy in NDs.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Emulsões/uso terapêutico , Nanoestruturas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doenças Priônicas/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Humanos
19.
Int J Pharm ; 578: 119098, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32018018

RESUMO

Nanoscale materials have contributed changing the way biomedical researchers address the biological and therapeutic limitations of conventional drugs and diagnostic agents. Thanks to a plethora of different materials and synthetic routes, particulate carriers can be designed to modify the half-life of compounds, alter their biodistribution and control the drug release profile, eventually providing an overall clinical benefit to patients. While around 50 nanoformulations (excluding biologics) are already on the market, several challenges still withhold them from unlocking their full translational potential. This review discusses the advantages and current hurdles in the use of nanopharmaceuticals, and describes the most important nanotechnological approaches which have been investigated so far. A focus is given on the record of clinical success and failures and current clinical trends. In an effort to identify opportunities and problems associated with each specific nanosystem, this manuscript underlines the need of a more product-oriented research, that can foster the progress of nanomedicines to the clinic.


Assuntos
Nanomedicina , Animais , Sistemas de Liberação de Medicamentos , Humanos , Nanomedicina/classificação , Nanoestruturas/classificação , Nanoestruturas/uso terapêutico
20.
Int J Nanomedicine ; 15: 537-552, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021193

RESUMO

Background: Synergistic chemoradiotherapy (CRT) has become a primary effective curative approach for many solid cancers. However, CRT is still associated with several obstacles, including the increases in side effects and systemic toxicity. Incorporating nanocarriers into CRT is a new and exciting approach to solve these obstacles. The purpose of the present study was to design a unique pH- and ultrasound-responsive perfluoropentane-encapsulated, paclitaxel (PTX)-loaded carboxymethyl chitosan nanodroplets (NDs) for combined imaging and synergistic CRT. Materials and Methods: The NDs were prepared by a homogenization/emulsion method. Their physicochemical properties, echogenicity and biocompatibility were evaluated. PTX-loaded NDs with a high loading efficiency and encapsulation efficiency were prepared and their pH-responsive drug release profile was determined by dialysis sack method. Then, PC3 cells were exposed to (1) PTX (4 µg/mL), (2) NDs (30 µg/mL), (3) PTX-loaded NDs (34 µg/mL), (4) RT (6 Gy), (5) RT (10 Gy), (6) combination of PTX (4 µg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy), (7) combination of NDs (30 µg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6Gy), (8) combination of PTX-loaded NDs (30 µg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy). 24 hrs later, CCK-8 assay, flow cytometry and migration assay were carried out to evaluate their therapeutic effects in CRT. Results: The desired NDs were successfully prepared, which were with round, spherical shapes, relatively smooth surfaces, core-shell structures and uniform in sizes (<300 nm with PDI<0.3 when at pH≧6.0). The NDs exhibited good abilities in pH-dependent charge conversion, biocompatibility and ultrasound contrast echogenicity. The in vitro drug release from PTX-loaded NDs (the highest loading efficiency and encapsulation efficiency were 20.35% and 91.58%) was pH dependent and exhibited an initial burst followed by a sustained drug release. The results of the CCK-8 assay, flow cytometry and migration assay all showed PTX-loaded NDs combined ultrasound and RT significantly enhanced cell responses in CRT. Conclusion: The pH- and ultrasound-responsive PTX-loaded NDs, which exhibited a high echogenicity, drug delivery ability and radiosensitization ability, could be a feasible option for combined imaging and novel enhancing approach in synergistic CRT.


Assuntos
Quitosana/análogos & derivados , Nanoestruturas/administração & dosagem , Paclitaxel/administração & dosagem , Linhagem Celular Tumoral , Quimiorradioterapia/métodos , Quitosana/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Fluorcarbonetos/química , Humanos , Concentração de Íons de Hidrogênio , Masculino , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Paclitaxel/química , Paclitaxel/farmacocinética , Tamanho da Partícula , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Ultrassonografia
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