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1.
Proc Natl Acad Sci U S A ; 117(44): 27141-27147, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33024017

RESUMO

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.


Assuntos
Infecções por Coronavirus/terapia , Citocinas/antagonistas & inibidores , Nanopartículas/uso terapêutico , Pneumonia Viral/terapia , Internalização do Vírus/efeitos dos fármacos , Animais , Betacoronavirus , Membrana Celular/química , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Células HEK293 , Humanos , Interleucina-6/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos ICR , Monócitos , Nanopartículas/química , Pandemias , Peptidil Dipeptidase A/metabolismo , Receptores de Citocinas/metabolismo , Células THP-1
2.
Nanomedicine (Lond) ; 15(24): 2411-2427, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32873192

RESUMO

There is an urgent need for safe and effective approaches to combat COVID-19. Here, we asked whether lessons learned from nanotoxicology and nanomedicine could shed light on the current pandemic. SARS-CoV-2, the causative agent, may trigger a mild, self-limiting disease with respiratory symptoms, but patients may also succumb to a life-threatening systemic disease. The host response to the virus is equally complex and studies are now beginning to unravel the immunological correlates of COVID-19. Nanotechnology can be applied for the delivery of antiviral drugs or other repurposed drugs. Moreover, recent work has shown that synthetic nanoparticles wrapped with host-derived cellular membranes may prevent virus infection. We posit that nanoparticles decorated with ACE2, the receptor for SARS-CoV-2, could be exploited as decoys to intercept the virus before it infects cells in the respiratory tract. However, close attention should be paid to biocompatibility before such nano-decoys are deployed in the clinic.


Assuntos
Infecções por Coronavirus/terapia , Nanomedicina/métodos , Pneumonia Viral/terapia , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Reposicionamento de Medicamentos/métodos , Humanos , Modelos Moleculares , Nanopartículas/uso terapêutico , Nanotecnologia/métodos , Pandemias , Peptidil Dipeptidase A/metabolismo , Peptidil Dipeptidase A/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo
3.
Int J Nanomedicine ; 15: 6113-6135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884267

RESUMO

The field of nanomedicine is constantly expanding. Since the first work dated in 1999, almost 28 thousand articles have been published, and more and more are published every year: just think that only in the last five years 20,855 have come out (source PUBMED) including original research and reviews. The goal of this review is to present the current knowledge about nanomedicine in Alzheimer's disease, a widespread neurodegenerative disorder in the over 60 population that deeply affects memory and cognition. Thus, after a brief introduction on the pathology and on the state-of-the-art research for NPs passing the BBB, special attention is placed to new targets that can enter the interest of nanoparticle designers and to new promising therapies. The authors performed a literature review limited to the last three years (2017-2020) of available studies with the intention to present only novel formulations or approaches where at least in vitro studies have been performed. This choice was made because, while limiting the sector to nanotechnology applied to Alzheimer, an organic census of all the relevant news is difficult to obtain.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Barreira Hematoencefálica/efeitos dos fármacos , Nanomedicina/métodos , Doença de Alzheimer/fisiopatologia , Animais , Barreira Hematoencefálica/fisiologia , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Medicina de Precisão , Transplante de Células-Tronco , Nanomedicina Teranóstica/métodos , Terapias em Estudo
4.
Exp Parasitol ; 218: 108008, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32979343

RESUMO

Acanthamoeba sp. is a free living amoeba that causes severe, painful and fatal infections, viz. Acanthamoeba keratitis and granulomatous amoebic encephalitis among humans. Antimicrobial chemotherapy used against Acanthamoeba is toxic to human cells and show side effects as well. Infections due to Acanthamoeba also pose challenges towards currently used antimicrobial treatment including resistance and transformation of trophozoites to resistant cyst forms that can lead to recurrence of infection. Therapeutic agents targeting central nervous system infections caused by Acanthamoeba should be able to cross blood-brain barrier. Nanoparticles based drug delivery put forth an effective therapeutic method to overcome the limitations of currently used antimicrobial chemotherapy. In recent years, various researchers investigated the effectiveness of nanoparticles conjugated drug and/or naturally occurring plant compounds against both trophozoites and cyst form of Acanthamoeba. In the current review, a reasonable effort has been made to provide a comprehensive overview of various nanoparticles tested for their efficacy against Acanthamoeba. This review summarizes the noteworthy details of research performed to elucidate the effect of nanoparticles conjugated drugs against Acanthamoeba.


Assuntos
Acanthamoeba/efeitos dos fármacos , Amebicidas/administração & dosagem , Nanopartículas/administração & dosagem , Acanthamoeba/crescimento & desenvolvimento , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Amebíase/tratamento farmacológico , Amebíase/mortalidade , Amebíase/parasitologia , Amebicidas/farmacologia , Amebicidas/uso terapêutico , Biguanidas/administração & dosagem , Biguanidas/farmacologia , Biguanidas/uso terapêutico , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Protozoárias do Sistema Nervoso Central/mortalidade , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Clorexidina/administração & dosagem , Clorexidina/farmacologia , Clorexidina/uso terapêutico , Sistemas de Liberação de Medicamentos , Imunocompetência , Hospedeiro Imunocomprometido , Encefalite Infecciosa/tratamento farmacológico , Encefalite Infecciosa/mortalidade , Encefalite Infecciosa/parasitologia , Nanopartículas/classificação , Nanopartículas/uso terapêutico , Trofozoítos/efeitos dos fármacos
5.
PLoS Pathog ; 16(9): e1008827, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886721

RESUMO

Global burden of cervical cancer, the most common cause of mortality caused by human papillomavirus (HPV), is expected to increase during the next decade, mainly because current alternatives for HPV vaccination and cervical cancer screening programs are costly to be established in low-and-middle income countries. Recently, we described the development of the broadly protective, thermostable vaccine antigen Trx-8mer-OVX313 based on the insertion of eight different minor capsid protein L2 neutralization epitopes into a thioredoxin scaffold from the hyperthermophilic archaeon Pyrococcus furiosus and conversion of the resulting antigen into a nanoparticle format (median radius ~9 nm) upon fusion with the heptamerizing OVX313 module. Here we evaluated whether the engineered thioredoxin scaffold, in addition to humoral immune responses, can induce CD8+ T-cell responses upon incorporation of MHC-I-restricted epitopes. By systematically examining the contribution of individual antigen modules, we demonstrated that B-cell and T-cell epitopes can be combined into a single antigen construct without compromising either immunogenicity. While CD8+ T-cell epitopes had no influence on B-cell responses, the L2 polytope (8mer) and OVX313-mediated heptamerization of the final antigen significantly increased CD8+ T-cell responses. In a proof-of-concept experiment, we found that vaccinated mice remained tumor-free even after two consecutive tumor challenges, while unvaccinated mice developed tumors. A cost-effective, broadly protective vaccine with both prophylactic and therapeutic properties represents a promising option to overcome the challenges associated with prevention and treatment of HPV-caused diseases.


Assuntos
Antígenos de Neoplasias , Antígenos Virais , Proteínas Arqueais , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer , Imunidade Celular/efeitos dos fármacos , Nanopartículas , Papillomaviridae , Vacinas contra Papillomavirus , Pyrococcus furiosus/química , Tiorredoxinas , Neoplasias do Colo do Útero/imunologia , Animais , Antígenos de Neoplasias/química , Antígenos de Neoplasias/farmacologia , Antígenos Virais/química , Antígenos Virais/farmacologia , Proteínas Arqueais/química , Proteínas Arqueais/farmacologia , Linfócitos T CD8-Positivos/patologia , Vacinas Anticâncer/química , Vacinas Anticâncer/farmacologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/farmacologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/farmacologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Papillomaviridae/química , Papillomaviridae/imunologia , Vacinas contra Papillomavirus/química , Vacinas contra Papillomavirus/farmacologia , Tiorredoxinas/química , Tiorredoxinas/farmacologia , Neoplasias do Colo do Útero/virologia
6.
Int J Nanomedicine ; 15: 5503-5516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801702

RESUMO

Objective: To comprehensively analyze the global scientific outputs of nanoparticles in pancreatic cancer research. Methods: Publications regarding the nanoparticles in pancreatic cancer research published from 1986 to 2019 were retrieved from the Web of Science Core Collection (WoSCC). Highly frequent keywords, publication years, journals, cited papers, cited journals and cited authors were identified using BICOMB software, and then a binary matrix and a co-word matrix were constructed. gCLUTO was used for double clustering of highly frequent journals. Co-citation analysis was performed using CiteSpace V software, including keywords, references, journals author or institution cooperation network. Results: A total of 1171 publications were included in this study. Publications mainly came from 10 countries, led by the US (n=470) and China (n=349). Among the top 20 journals ranked by the number of citations, nanoscience nanotechnology was the leader with 300. Cluster analysis of citation network identified 12 co-citation clusters, headed by "stromal barrier" and "emerging inorganic nanomaterial". Conclusion: Our findings reveal the research performance and intellectual structure of the nanoparticles in pancreatic cancer research, which may help researchers understand the research trends and hotspots in this field.


Assuntos
Pesquisa Biomédica/estatística & dados numéricos , Nanopartículas/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Publicações Seriadas/estatística & dados numéricos , Bibliometria , China , Análise por Conglomerados , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanotecnologia , Software , Estados Unidos
7.
Int J Nanomedicine ; 15: 5839-5853, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848393

RESUMO

Background: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance. However, due to the variable pharmacokinetics of FKA and PTX, the conventional cocktail combination in clinics may cause uncertainty of treatment efficacy in vivo. Materials and Methods: To synergistically elevate the anti-cancer activity of PTX and FKA in vivo, the national medical products administration (NMPA) approved sodium aescinate (Aes) was utilized to stabilize hydrophobic PTX and FKA to form polymer-free twin like PTX-A nanoparticles (NPs) and FKA-A NPs. Results: The resulting nanoparticles prepared simply by nanoprecipitation possessed similar particle size, good stability and ultrahigh drug loadings of up to 50%. With the aid of Aes, these two drugs accumulated in tumor tissue by passive targeting and were efficiently taken up by A549/T cells; this resulted in significant suppression of tumor growth in A549/T homograft mice at a low PTX dose (2.5 mg·kg-1). Synergistic effects and reversed PTX resistance were achieved by the combination of PTX-A NPs and FKA-A NPs by inhibiting P-gp expression in tumor cells. Conclusion: Using NMPA-approved Aes to prepare twin-like nanoparticles without introducing any new materials provides an efficient platform for combination chemotherapy and clinical translation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas/química , Paclitaxel/farmacologia , Saponinas/química , Triterpenos/química , Células A549 , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Linhagem Celular Tumoral , Chalcona/administração & dosagem , Chalcona/análogos & derivados , Chalcona/farmacocinética , Estabilidade de Medicamentos , Sinergismo Farmacológico , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Tamanho da Partícula , Polímeros/química , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Int J Nanomedicine ; 15: 4501-4521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606691

RESUMO

Purpose: Elevation of blood homocysteine (Hcy) level (hyperhomocysteinemia) is a risk factor for cardiovascular disorders and is closely associated with endothelial dysfunction. The present study aims to investigate the protective effect and underlying mechanism of nanoscale selenium (Nano-Se) in Hcy-mediated vascular endothelial cell dysfunction in vitro and in vivo. Materials and Methods: By incubating vascular endothelial cells with exogenous Hcy and generating hyperhomocysteinemic rat model, the effects of Nano-Se on hyperhomocysteinemia-mediated endothelial dysfunction and its essential mechanisms were investigated. Results: Nano-Se inhibited Hcy-induced mitochondrial oxidative damage and apoptosis by preventing the downregulation of glutathione peroxidase enzyme 1 and 4 (GPX1, GPX4) in the vascular endothelial cells, thus effectively prevented the vascular damage in vitro and in vivo in the hyperhomocysteinemic rats. Nano-Se possessed similar protective effects but lower toxicity against Hcy in vascular endothelial cells when compared with other forms of Se. Conclusion: The application of Nano-Se could serve as a novel promising strategy against Hcy-mediated vascular dysfunction with reduced risk of Se toxicity.


Assuntos
Antioxidantes/farmacologia , Células Endoteliais da Veia Umbilical Humana/patologia , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/fisiopatologia , Nanopartículas/uso terapêutico , Selênio/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Glutationa Peroxidase/metabolismo , Homocisteína , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas/ultraestrutura , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Selênio/farmacologia
9.
Nat Commun ; 11(1): 3638, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686667

RESUMO

Surface charge plays a fundamental role in determining the fate of a nanoparticle, and any encapsulated contents, in vivo. Herein, we describe, and visualise in real time, light-triggered switching of liposome surface charge, from neutral to cationic, in situ and in vivo (embryonic zebrafish). Prior to light activation, intravenously administered liposomes, composed of just two lipid reagents, freely circulate and successfully evade innate immune cells present in the fish. Upon in situ irradiation and surface charge switching, however, liposomes rapidly adsorb to, and are taken up by, endothelial cells and/or are phagocytosed by blood resident macrophages. Coupling complete external control of nanoparticle targeting together with the intracellular delivery of encapsulated (and membrane impermeable) cargos, these compositionally simple liposomes are proof that advanced nanoparticle function in vivo does not require increased design complexity but rather a thorough understanding of the fundamental nano-bio interactions involved.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Lipossomos/química , Nanopartículas/química , Animais , Cátions/metabolismo , Lipossomos/farmacologia , Lipossomos/uso terapêutico , Macrófagos , Membranas/metabolismo , Nanomedicina/métodos , Nanopartículas/uso terapêutico , Fagocitose , Peixe-Zebra
10.
Nat Commun ; 11(1): 3637, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686685

RESUMO

We report a strategy to boost Fenton reaction triggered by an exogenous circularly polarized magnetic field (MF) to enhance ferroptosis-like cell-death mediated immune response, as well as endow a responsive MRI capability by using a hybrid core-shell vesicles (HCSVs). HCSVs are prepared by loading ascorbic acid (AA) in the core and poly(lactic-co-glycolic acid) shell incorporating iron oxide nanocubes (IONCs). MF triggers the release of AA, resulting in the increase of ferrous ions through the redox reaction between AA and IONCs. A significant tumor suppression is achieved by Fenton reaction-mediated ferroptosis-like cell-death. The oxidative stress induced by the Fenton reaction leads to the exposure of calreticulin on tumor cells, which leads to dendritic cells maturation and the infiltration of cytotoxic T lymphocytes in tumor. Furthermore, the depletion of ferric ions during treatment enables monitoring of the Fe reaction in MRI-R2* signal change. This strategy provides a perspective on ferroptosis-based immunotherapy.


Assuntos
Ferroptose/efeitos dos fármacos , Campos Magnéticos , Nanopartículas de Magnetita , Neoplasias/terapia , Animais , Ácido Ascórbico/farmacologia , Calreticulina/metabolismo , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Compostos Férricos/química , Imunoterapia/métodos , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/imunologia , Estresse Oxidativo , Linfócitos T Citotóxicos/metabolismo
11.
Nat Commun ; 11(1): 3712, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709842

RESUMO

Metal hydrides have been rarely used in biomedicine. Herein, we fabricate titanium hydride (TiH1.924) nanodots from its powder form via the liquid-phase exfoliation, and apply these metal hydride nanodots for effective cancer treatment. The liquid-phase exfoliation is an effective method to synthesize these metal hydride nanomaterials, and its efficiency is determined by the matching of surface energy between the solvent and the metal hydrides. The obtained TiH1.924 nanodots can produce reactive oxygen species (ROS) under ultrasound, presenting a highly efficient sono-sensitizing effect. Meanwhile, TiH1.924 nanodots with strong near-infrared (NIR) absorbance can serve as a robust photothermal agent. By using the mild photothermal effect to enhance intra-tumoral blood flow and improve tumor oxygenation, a remarkable synergistic therapeutic effect is achieved in the combined photothermal-sonodynamic therapy. Importantly, most of these TiH1.924 nanodots can be cleared out from the body. This work presents the promises of functional metal hydride nanomaterials for biomedical applications.


Assuntos
Antineoplásicos/química , Nanopartículas/uso terapêutico , Nanoestruturas/química , Titânio/química , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanotecnologia , Espécies Reativas de Oxigênio , Difração de Raios X
12.
Nat Biotechnol ; 38(7): 845-855, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32601435

RESUMO

Genome editing has the potential to treat an extensive range of incurable monogenic and complex diseases. In particular, advances in sequence-specific nuclease technologies have dramatically accelerated the development of therapeutic genome editing strategies that are based on either the knockout of disease-causing genes or the repair of endogenous mutated genes. These technologies are progressing into human clinical trials. However, challenges remain before the therapeutic potential of genome editing can be fully realized. Delivery technologies that have serendipitously been developed over the past couple decades in the protein and nucleic acid delivery fields have been crucial to genome editing success to date, including adeno-associated viral and lentiviral vectors for gene therapy and lipid nanoparticle and other non-viral vectors for nucleic acid and protein delivery. However, the efficiency and tissue targeting capabilities of these vehicles must be further improved. In addition, the genome editing enzymes themselves need to be optimized, and challenges regarding their editing efficiency, specificity and immunogenicity must be addressed. Emerging protein engineering and synthetic chemistry approaches can offer solutions and enable the development of safe and efficacious clinical genome editing.


Assuntos
Sistemas CRISPR-Cas/genética , Edição de Genes/tendências , Doenças Genéticas Inatas/terapia , Terapia Genética , Doenças Genéticas Inatas/genética , Vetores Genéticos/genética , Vetores Genéticos/uso terapêutico , Humanos , Nanopartículas/uso terapêutico , Engenharia de Proteínas
13.
Int J Nanomedicine ; 15: 4453-4470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32617003

RESUMO

Background: Exosomes are small vesicles produced by almost all cells in the body and found in all biofluids. Cancer cell-derived exosomes are known to have distinct, measurable signatures, applicable for early cancer diagnosis. Despite the present bibliometric studies on "Cancer detection" and "Nanoparticles", no single study exists to deal with "Exosome" bibliometric study. Methods: This bibliometric work investigated the publication trends of "Exosomes" nanoparticles and its application in cancer detection, for the literature from 2008 to July 2019. The data were collected from the Web of Science Core Collection. There were variant visual maps generated to show annual publication, most- relevant authors, sources, countries, topics and keywords. The network analysis of these studies was investigated to evaluate the research trends in the field of exosomes. In addition, the data were qualitatively analyzed according to 22 top-cited articles, illustrating the frequently used subjects and methods in exosomes research area. Results: The results showed that the documents in this field have improved the citation rate. The top-relevant papers are mostly published in Scientific Reports journal which has lost its popularity after 2017, while today, Analytical Chemistry is leading in publishing the most articles related to exosomes. The documents containing keywords of plasma, cells, cancer, biomarkers, and vesicles as keywords plus, are more likely to be published in PLoS One journal. The clustering of the keywords network showed that the keyword theme of "extracellular vesicles" has the highest centrality rate. In global research, USA is the most corresponding country, followed by China, Korea and Australia. Based on the qualitative analysis, the published documents with at least 50 citations have used exosome release, cargo, detection, purification and secretion, as their targets and applied cell culture or isolation as their methods. Conclusion: The bibliometric study on exosomes nanoparticles for cancer detection provides a clear vision of the future research direction and identifies the potential opportunities and challenges. This may lead new researchers to select the proper subfields in exosome-related research fields.


Assuntos
Bibliometria , Exossomos , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico , Publicações Seriadas/estatística & dados numéricos , Austrália , China , Humanos , República da Coreia
14.
Int J Nanomedicine ; 15: 4639-4657, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636623

RESUMO

Background: ß-Glucosidase (ß-Glu) can activate amygdalin to kill prostate cancer cells, but the poor specificity of this killing effect may cause severe general toxicity in vivo, limiting the practical clinical application of this approach. Materials and Methods: In this study, starch-coated magnetic nanoparticles (MNPs) were successively conjugated with ß-Glu and polyethylene glycol (PEG) by chemical coupling methods. Cell experiments were used to confirm the effects of immobilized ß-Glu on amygdalin-mediated prostate cancer cell death in vitro. Subcutaneous xenograft models were used to carry out the targeting experiment and magnetically directed enzyme/prodrug therapy (MDEPT) experiment in vivo. Results: Immobilized ß-Glu activated amygdalin-mediated prostate cancer cell death. Tumor-targeting studies showed that PEG modification increased the accumulation of ß-Glu-loaded nanoparticles in targeted tumor tissue subjected to an external magnetic field and decreased the accumulation of the nanoparticles in the liver and spleen. Based on an enzyme activity of up to 134.89 ± 14.18mU/g tissue in the targeted tumor tissue, PEG-ß-Glu-MNP/amygdalin combination therapy achieved targeted activation of amygdalin and tumor growth inhibition in C57BL/6 mice bearing RM1 xenografts. Safety evaluations showed that this strategy had some impact on liver and heart function but did not cause obvious organ damage. Conclusion: All findings indicate that this magnetically directed enzyme/prodrug therapy strategy has the potential to become a promising new approach for targeted therapy of prostate cancer.


Assuntos
Amigdalina/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Nanopartículas/química , Neoplasias da Próstata/tratamento farmacológico , beta-Glucosidase/metabolismo , Animais , Linhagem Celular Tumoral , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Humanos , Campos Magnéticos , Fenômenos Magnéticos , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/uso terapêutico , Polietilenoglicóis/química , Pró-Fármacos/farmacologia , Neoplasias da Próstata/patologia , Amido/química , beta-Glucosidase/química
15.
Theranostics ; 10(13): 5932-5942, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-501783

RESUMO

On the 30th of January 2020, the World Health Organization fired up the sirens against a fast spreading infectious disease caused by a newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and gave this disease the name COVID-19. While there is currently no specific treatment for COVID-19, several off label drugs approved for other indications are being investigated in clinical trials across the globe. In the last decade, theranostic nanoparticles were reported as promising tool for efficiently and selectively deliver therapeutic moieties (i.e. drugs, vaccines, siRNA, peptide) to target sites of infection. In addition, they allow monitoring infectious sides and treatment responses using noninvasive imaging modalities. While intranasal delivery was proposed as the preferred administration route for therapeutic agents against viral pulmonary diseases, NP-based delivery systems offer numerous benefits to overcome challenges associated with mucosal administration, and ensure that these agents achieve a concentration that is many times higher than expected in the targeted sites of infection while limiting side effects on normal cells. In this article, we have shed light on the promising role of nanoparticles as effective carriers for therapeutics or immune modulators to help in fighting against COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Nanopartículas/uso terapêutico , Pneumonia Viral/terapia , Nanomedicina Teranóstica/métodos , Administração Intranasal , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanopartículas/administração & dosagem , Nanopartículas/química , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Internalização do Vírus/efeitos dos fármacos
16.
Theranostics ; 10(13): 5932-5942, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483428

RESUMO

On the 30th of January 2020, the World Health Organization fired up the sirens against a fast spreading infectious disease caused by a newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and gave this disease the name COVID-19. While there is currently no specific treatment for COVID-19, several off label drugs approved for other indications are being investigated in clinical trials across the globe. In the last decade, theranostic nanoparticles were reported as promising tool for efficiently and selectively deliver therapeutic moieties (i.e. drugs, vaccines, siRNA, peptide) to target sites of infection. In addition, they allow monitoring infectious sides and treatment responses using noninvasive imaging modalities. While intranasal delivery was proposed as the preferred administration route for therapeutic agents against viral pulmonary diseases, NP-based delivery systems offer numerous benefits to overcome challenges associated with mucosal administration, and ensure that these agents achieve a concentration that is many times higher than expected in the targeted sites of infection while limiting side effects on normal cells. In this article, we have shed light on the promising role of nanoparticles as effective carriers for therapeutics or immune modulators to help in fighting against COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Nanopartículas/uso terapêutico , Pneumonia Viral/terapia , Nanomedicina Teranóstica/métodos , Administração Intranasal , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanopartículas/administração & dosagem , Nanopartículas/química , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Internalização do Vírus/efeitos dos fármacos
17.
Int J Nanomedicine ; 15: 3953-3964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581539

RESUMO

Objective: To construct an ideal theranostic nanoplatform (LIP3); to clarify its physicochemical properties; to confirm its characteristics of dual-modality imaging, active-targeting, and cascade amplification therapy for mammary carcinoma; and to perform a preliminary exploration of the cytotoxicity mechanism. Design: A self-prepared liposome nanosystem, LIP3, can actively target 4T1 cells because the surface is linked with C-RGD. Haematoporphyrin monomethyl ether (HMME), an excellent sonosensitizer entrapped in the lipid bilayer, can function in photoacoustic imaging. Low-intensity focused ultrasound (LIFU) of ultrasound-targeted microbubble destruction (UTMD) promotes localized drug delivery into tumours because PFH, a phase-change substance, is loaded in the LIP3 core, achieving visualization of targeted drug release, and sonodynamic therapy (SDT) can kill tumour cells. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging and precise treatment. Results: The self-prepared lipid nanosystem, LIP3, meets the above expectations and has ideal physicochemical properties, with a regular sphere with uniform distribution. Contrast-enhanced ultrasound (CEUS), photoacoustic imaging, and bimodal imaging were effective in vitro. In 4T1 cell experiments, the cell capacity was as high as 42.9%, and the cytotoxicity to 4T1 was more than 5 times that of LIP1 (containing AQ4N only) and more than 2 times that of LIP2 (containing only HMME), achieving comparable results as cascade therapy for mammary cancer. Conclusion: LIP3, a theranostic nanoplatform, was successfully constructed and conformed to the physicochemical characterization of ideal nanoparticles, with active-targeting, dual-modality imaging, visualized drug release, and precise treatment under the action of LIFU. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging, and precise cascade treatment. This unique theranostic NPS with multiple capabilities is expected to be a favourable anti-cancer method in the future.


Assuntos
Neoplasias da Mama/terapia , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Animais , Neoplasias da Mama/diagnóstico por imagem , Linhagem Celular Tumoral , Meios de Contraste/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Hematoporfirinas/química , Humanos , Lipídeos/química , Lipossomos/química , Camundongos Nus , Nanopartículas/uso terapêutico , Oligopeptídeos/química , Coelhos , Ultrassonografia de Intervenção/métodos
19.
Int J Nanomedicine ; 15: 2699-2715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368050

RESUMO

Purpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29-39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes' expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.


Assuntos
Antivirais/farmacologia , Curcumina/farmacologia , Hepacivirus/efeitos dos fármacos , Nanopartículas/química , Antivirais/química , Linhagem Celular , Quitosana/química , Curcumina/administração & dosagem , Curcumina/química , Genótipo , Hepacivirus/genética , Hepacivirus/patogenicidade , Humanos , Neoplasias Hepáticas/virologia , Nanopartículas/uso terapêutico , Proteínas do Core Viral/metabolismo , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
20.
Nanomedicine (Lond) ; 15(15): 1501-1512, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32378459

RESUMO

Nanotechnology and nanomedicine have excellent potential in dealing with a range of different health problems, including viruses, which are considered to be a serious challenge in the medical field. Application of nanobiotechnology could represent a new avenue for the treatment or disinfection of viruses. There is increasing concern regarding the control of coronaviruses, among these, Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus-2 are well known and dangerous examples. This article aims to provide an overview of recent studies on the effectiveness of nanoparticles as diagnostic or antiviral tools against coronaviruses. The possibilities of effectively using nanomaterials as vaccines and nanosensors in this field are also presented.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Nanopartículas/uso terapêutico , Animais , Antivirais/análise , Técnicas Biossensoriais/métodos , Coronavirus/efeitos dos fármacos , Coronavirus/isolamento & purificação , Infecções por Coronavirus/prevenção & controle , Humanos , Nanomedicina/métodos , Nanopartículas/análise , Nanotecnologia/métodos , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia
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