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1.
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
2.
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
3.
Nat Commun ; 11(1): 4615, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934241

RESUMO

Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropic detergent (MSDH) and an autophagy inhibitor (Lys05) are hybridised to develop bisaminoquinoline derivatives that can intrinsically form nanoassemblies. The selected BAQ12 and BAQ13 ONNs are highly effective in inducing lysosomal disruption, lysosomal dysfunction and autophagy blockade and exhibit 30-fold higher antiproliferative activity than hydroxychloroquine used in clinical trials. These single-drug nanoparticles demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these BAQ ONNs have enormous potential to improve cancer therapy.


Assuntos
Aminoquinolinas/química , Antineoplásicos/química , Sistemas de Liberação de Medicamentos/métodos , Lisossomos/efeitos dos fármacos , Nanomedicina/métodos , Neoplasias/tratamento farmacológico , Aminoquinolinas/administração & dosagem , Aminoquinolinas/farmacocinética , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/instrumentação , Humanos , Nanomedicina/instrumentação , Nanopartículas/química , Neoplasias/fisiopatologia , Ratos , Ratos Sprague-Dawley
4.
Proc Natl Acad Sci U S A ; 117(37): 22639-22648, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32900936

RESUMO

Despite an abundant literature on gold nanoparticles use for biomedicine, only a few of the gold-based nanodevices are currently tested in clinical trials, and none of them are approved by health agencies. Conversely, ionic gold has been used for decades to treat human rheumatoid arthritis and benefits from 70-y hindsight on medical use. With a view to open up new perspectives in gold nanoparticles research and medical use, we revisit here the literature on therapeutic gold salts. We first summarize the literature on gold salt pharmacokinetics, therapeutic effects, adverse reactions, and the present repurposing of these ancient drugs. Owing to these readings, we evidence the existence of a common metabolism of gold nanoparticles and gold ions and propose to use gold salts as a "shortcut" to assess the long-term effects of gold nanoparticles, such as their fate and toxicity, which remain challenging questions nowadays. Moreover, one of gold salts side effects (i.e., a blue discoloration of the skin exposed to light) leads us to propose a strategy to biosynthesize large gold nanoparticles from gold salts using light irradiation. These hypotheses, which will be further investigated in the near future, open up new avenues in the field of ionic gold and gold nanoparticles-based therapies.


Assuntos
Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Nanomedicina/tendências , Artrite Reumatoide/tratamento farmacológico , Ouro/efeitos adversos , Humanos , Nanopartículas Metálicas/efeitos adversos , Nanomedicina/métodos
5.
Nat Commun ; 11(1): 4124, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807787

RESUMO

In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. Here, we describe the concept of augmented synthetic lethality (ASL): depletion of a third gene product enhances a pre-existing synthetic lethal combination. We show that loss of the DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-tumor responses alone and in combination with cisplatin chemotherapy. Delivery of siRNA-peptide nanoplexes co-targeting MK2 and XPA to pre-existing p53-deficient tumors in a highly aggressive, immunocompetent mouse model of lung adenocarcinoma improves long-term survival and cisplatin response beyond those of the synthetic lethal p53 mutant/MK2 combination alone. These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment.


Assuntos
Pontos de Checagem do Ciclo Celular/fisiologia , Reparo do DNA/fisiologia , Animais , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Dano ao DNA/genética , Dano ao DNA/fisiologia , Reparo do DNA/genética , Células HCT116 , Humanos , Immunoblotting , Camundongos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanomedicina/métodos , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
6.
Int J Nanomedicine ; 15: 4793-4810, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764921

RESUMO

Background: Platinum resistance is a major challenge in the management of ovarian cancer. Even low levels of acquired resistance at the cellular level lead to impaired response to cisplatin. In ovarian cancer intraperitoneal therapy, nanoparticle formulation can improve the cisplatin's pharmacokinetics and safety profile. Purpose: This work aimed to investigate the chemo-sensitivity of ovarian cancer SKOV3 cells upon short-term (72h) single treatment of cisplatin and cisplatin-loaded biodegradable nanoparticles (Cis-NP). The aim was then to determine the therapeutic properties of Cis-NP in vivo using a SKOV3-luc cells' xenograft model in mice. Methods: Cell cytotoxicity was assessed after the exposure of the cell culture to cisplatin or Cis-NP. The effect of treatments on EMT and CSC-like phenotype was studied by analyzing a panel of markers by flow cytometry. Intracellular platinum concentration was determined by inductively coupled plasma mass spectrometry (ICS-MS), and gene expression was evaluated by RNAseq analysis. The efficacy of intraperitoneal chemotherapy was evaluated in a SKOV3-luc cells' xenograft model in mice, through a combination of bioluminescence imaging, histological, and immunohistochemical analyses. Results: We observed in vitro that short-term treatment of cisplatin has a critical role in determining the potential induction of chemoresistance, and a nanotechnology-based drug delivery system can modulate it. The RNAseq analysis underlines a protective effect of nanoparticle system according to their ability to down-regulate several genes involved in chemoresistance, cell proliferation, and apoptosis. The highest intracellular platinum concentration obtained with Cis-NP treatment significantly improved the efficacy. Consistent with in vitro results, we found that Cis-NP treatment in vivo can significantly reduce tumor burden and aggressiveness compared to the free drug. Conclusion: Nanoparticle-mediated cisplatin delivery may serve as an intracellular depot impacting the cisplatin pharmacodynamic performance at cellular levels. These features may contribute to improving the drawbacks of conventional intraperitoneal therapy, and therefore will require further investigations in vivo.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Portadores de Fármacos/química , Espaço Intracelular/metabolismo , Nanomedicina/métodos , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/química , Cisplatino/metabolismo , Cisplatino/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Nat Biomed Eng ; 4(7): 717-731, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32632229

RESUMO

The rapid elimination of nanoparticles from the bloodstream by the mononuclear phagocyte system limits the activity of many nanoparticle formulations. Here, we show that inducing a slight and transient depletion of erythrocytes in mice (~5% decrease in haematocrit) by administrating a low dose (1.25 mg kg-1) of allogeneic anti-erythrocyte antibodies increases the circulation half-life of a range of short-circulating and long-circulating nanoparticle formulations by up to 32-fold. Treatment of the animals with anti-erythrocyte antibodies significantly improved the targeting of CD4+ cells in vivo with fluorescent anti-CD4-antibody-conjugated nanoparticles, the magnetically guided delivery of ferrofluid nanoparticles to subcutaneous tumour allografts and xenografts, and the treatment of subcutaneous tumour allografts with magnetically guided liposomes loaded with doxorubicin and magnetite or with clinically approved 'stealthy' doxorubicin liposomes. The transient and partial blocking of the mononuclear phagocyte system may enhance the performance of a wide variety of nanoparticle drugs.


Assuntos
Circulação Sanguínea/fisiologia , Portadores de Fármacos/farmacologia , Eritrócitos , Nanomedicina/métodos , Animais , Anticorpos , Linfócitos T CD4-Positivos , Citocinas/metabolismo , Doxorrubicina/análogos & derivados , Eritrócitos/imunologia , Feminino , Meia-Vida , Xenoenxertos , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Nanopartículas/administração & dosagem , Polietilenoglicóis , Ratos , Ratos Wistar , Sepse/tratamento farmacológico
8.
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
9.
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
10.
J Control Release ; 326: 164-171, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32681950

RESUMO

The situation of the COVID-19 pandemic reminds us that we permanently need high-value flexible solutions to urgent clinical needs including simplified diagnostic technologies suitable for use in the field and for delivering targeted therapeutics. From our perspective nanotechnology is revealed as a vital resource for this, as a generic platform of technical solutions to tackle complex medical challenges. It is towards this perspective and focusing on nanomedicine that we take issue with Prof Park's recent editorial published in the Journal of Controlled Release. Prof. Park argued that in the last 15 years nanomedicine failed to deliver the promised innovative clinical solutions to the patients (Park, K. The beginning of the end of the nanomedicine hype. Journal of Controlled Release, 2019; 305, 221-222 [1]. We, the ETPN (European Technology Platform on Nanomedicine) [2], respectfully disagree. In fact, the more than 50 formulations currently in the market, and the recent approval of 3 key nanomedicine products (e. g. Onpattro, Hensify and Vyxeos), have demonstrated that the nanomedicine field is concretely able to design products that overcome critical barriers in conventional medicine in a unique manner, but also to deliver within the cells new drug-free therapeutic effects by using pure physical modes of action, and therefore make a difference in patients lives. Furthermore, the >400 nanomedicine formulations currently in clinical trials are expecting to bring novel clinical solutions (e.g. platforms for nucleic acid delivery), alone or in combination with other key enabling technologies to the market, including biotechnologies, microfluidics, advanced materials, biomaterials, smart systems, photonics, robotics, textiles, Big Data and ICT (information & communication technologies) more generally. However, we agree with Prof. Park that " it is time to examine the sources of difficulty in clinical translation of nanomedicine and move forward ". But for reaching this goal, the investments to support clinical translation of promising nanomedicine formulations should increase, not decrease. As recently encouraged by EMA in its roadmap to 2025, we should create more unity through a common knowledge hub linking academia, industry, healthcare providers and hopefully policy makers to reduce the current fragmentation of the standardization and regulatory body landscape. We should also promote a strategy of cross-technology innovation, support nanomedicine development as a high value and low-cost solution to answer unmet medical needs and help the most promising innovative projects of the field to get better and faster to the clinic. This global vision is the one that the ETPN chose to encourage for the last fifteen years. All actions should be taken with a clear clinical view in mind, " without any fanfare", to focus "on what matters in real life", which is the patient and his/her quality of life. This ETPN overview of achievements in nanomedicine serves to reinforce our drive towards further expanding and growing the maturity of nanomedicine for global healthcare, accelerating the pace of transformation of its great potential into tangible medical breakthroughs.


Assuntos
Sistemas de Liberação de Medicamentos , Nanomedicina , Animais , Ensaios Clínicos como Assunto , Infecções por Coronavirus/terapia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanomedicina/métodos , Nanotecnologia/métodos , Neoplasias/terapia , Pandemias , Pneumonia Viral/terapia
11.
Bioconjug Chem ; 31(8): 1873-1882, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32639742

RESUMO

With the current COVID-19 outbreak, it has become essential to develop efficient methods for the treatment and detection of this virus. Among the new approaches that could be tested, that relying on nanotechnology finds one of its main grounds in the similarity between nanoparticle (NP) and coronavirus (COV) sizes, which promotes NP-COV interactions. Since COVID-19 is very recent, most studies in this field have focused on other types of coronavirus than COVID-19, such as those involved in MERS or SARS diseases. Although their number is limited, they have led to promising results on various COV using a wide range of different types of nanosystems, e.g., nanoparticles, quantum dos, or nanoassemblies of polymers/proteins. Additional efforts deserve to be spent in this field to consolidate these findings. Here, I first summarize the different nanotechnology-based methods used for COV detection, i.e., optical, electrical, or PCR ones, whose sensitivity was improved by the presence of nanoparticles. Furthermore, I present vaccination methods, which comprise nanoparticles used either as adjuvants or as active principles. They often yield a better-controlled immune response, possibly due to an improved antigen presentation/processing than in non-nanoformulated vaccines. Certain antiviral approaches also took advantage of nanoparticle uses, leading to specific mechanisms such as the blocking of virus replication at the cellular level or the reduction of a COV induced apoptotic cellular death.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Nanomedicina/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Antivirais/farmacologia , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia
12.
Int J Nanomedicine ; 15: 4705-4716, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636626

RESUMO

Purpose: Ultra-small gold nanoclusters (AuNCs), as emerging fluorescent nanomaterials with excellent biocompatibility, have been widely investigated for in vivo biomedical applications. However, their effects in guiding osteogenic differentiation have not been investigated, which are important for osteoporosis therapy and bone regeneration. Herein, for the first time, lysozyme-protected AuNCs (Lys-AuNCs) are used to stimulate osteogenic differentiation, which have the potential for the treatment of bone disease. Methods: Proliferation of MC3T3E-1 is important for osteogenic differentiation. First, the proliferation rate of MC3T3E-1 was studied by Cell Counting Kit-8 (CCK8) assays. Signaling pathways of PI3K/Akt play central roles in controlling proliferation throughout the body. The expression of PI3K/Akt was investigated in the presence of lysozyme, and lysozyme-protected AuNCs (Lys-AuNCs) by Western blot (WB) and intracellular cell imaging to evacuate the osteogenic differentiation mechanisms. Moreover, the formation of osteoclasts (OC) plays a negative role in the differentiation of osteoblasts. Nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) signaling pathways are used to understand the negative influence of the osteogenic differentiation by the investigation of Raw 264.7 cell line. Raw 264.7 (murine macrophage-like) cells and NIH/3T3 (mouse fibroblast) cells were treated with tyloxapol, and the cell viability was assessed. Raw 264.7 cells have also been used for in vitro studies, on understanding the osteoclast formation and function. The induced osteoclasts were identified by TRAP confocal fluorescence imaging. These key factors in osteoclast formation, such as (NFATc-1, c-Fos, V-ATPase-2 and CTSK), were investigated by Western blot. Results: Based on the above investigation, Lys-AuNCs were found to promote osteogenic differentiation and decrease osteoclast activity. It is noteworthy that the lysozyme (protected template), AuNPs, or the mixture of Lysozyme and AuNPs have negligible effects on osteoblastic differentiation compared to Lys-AuNCs. Conclusion: This study opens up a novel avenue to develop a new gold nanomaterial for promoting osteogenic differentiation. The possibility of using AuNCs as nanomedicines for the treatment of osteoporosis can be expected.


Assuntos
Nanopartículas Metálicas/química , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Ouro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Camundongos , Muramidase/química , Muramidase/metabolismo , Fatores de Transcrição NFATC/metabolismo , Nanomedicina/métodos , Osteoblastos/citologia , Osteoclastos/citologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7
13.
Nanomedicine (Lond) ; 15(21): 2085-2102, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32723142

RESUMO

The COVID-19 pandemic caused by the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) puts the world in an unprecedented crisis, leaving behind huge human losses and deep socioeconomic damages. Due to the lack of specific treatment against SARS-CoV-2, effective vaccines and antiviral agents are urgently needed to properly restrain the COVID-19 pandemic. Repositioned drugs such as remdesivir have revealed a promising clinical efficacy against COVID-19. Interestingly, nanomedicine as a promising therapeutic approach could effectively help win the battle between coronaviruses (CoVs) and host cells. This review discusses the potential therapeutic approaches, in addition to the contribution of nanomedicine against CoVs in the fields of vaccination, diagnosis and therapy.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Nanomedicina/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Reposicionamento de Medicamentos , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Humanos , Nanotecnologia/métodos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Vacinas Sintéticas/farmacologia , Vacinas Virais/farmacologia
14.
Proc Natl Acad Sci U S A ; 117(31): 18719-18728, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32690692

RESUMO

CD4-based decoy approaches against HIV-1 are attractive options for long-term viral control, but initial designs, including soluble CD4 (sCD4) and CD4-Ig, were ineffective. To evaluate a therapeutic that more accurately mimics HIV-1 target cells compared with monomeric sCD4 and dimeric CD4-Ig, we generated virus-like nanoparticles that present clusters of membrane-associated CD4 (CD4-VLPs) to permit high-avidity binding of trimeric HIV-1 envelope spikes. In neutralization assays, CD4-VLPs were >12,000-fold more potent than sCD4 and CD4-Ig and >100-fold more potent than the broadly neutralizing antibody (bNAb) 3BNC117, with >12,000-fold improvements against strains poorly neutralized by 3BNC117. CD4-VLPs also neutralized patient-derived viral isolates that were resistant to 3BNC117 and other bNAbs. Intraperitoneal injections of CD4-CCR5-VLP produced only subneutralizing plasma concentrations in HIV-1-infected humanized mice but elicited CD4-binding site mutations that reduced viral fitness. All mutant viruses showed reduced sensitivity to sCD4 and CD4-Ig but remained sensitive to neutralization by CD4-VLPs in vitro. In vitro evolution studies demonstrated that CD4-VLPs effectively controlled HIV-1 replication at neutralizing concentrations, and viral escape was not observed. Moreover, CD4-VLPs potently neutralized viral swarms that were completely resistant to CD4-Ig, suggesting that escape pathways that confer resistance against conventional CD4-based inhibitors are ineffective against CD4-VLPs. These findings suggest that therapeutics that mimic HIV-1 target cells could prevent viral escape by exposing a universal vulnerability of HIV-1: the requirement to bind CD4 on a target cell. We propose that therapeutic and delivery strategies that ensure durable bioavailability need to be developed to translate this concept into a clinically feasible functional cure therapy.


Assuntos
Antígenos CD4 , HIV-1 , Nanopartículas , Vírion , Fármacos Anti-HIV , Antígenos CD4/química , Antígenos CD4/metabolismo , Linhagem Celular , HIV-1/química , HIV-1/genética , HIV-1/metabolismo , Humanos , Mimetismo Molecular , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/metabolismo , Vírion/química , Vírion/metabolismo
15.
Cancer Sci ; 111(9): 3164-3173, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32589345

RESUMO

Structural DNA nanotechnology enables DNA to be used as nanomaterials for novel nanostructure construction with unprecedented functionalities. Artificial DNA nanostructures can be designed and generated with precisely controlled features, resulting in its utility in bionanotechnological and biomedical applications. A tetrahedral DNA nanostructure (TDN), the most popular DNA nanostructure, with high stability and simple synthesis procedure, is a promising candidate as nanocarriers in drug delivery and bioimaging platforms, particularly in precision medicine as well as diagnosis for cancer therapy. Recent evidence collectively indicated that TDN successfully enhanced cancer therapeutic efficiency both in vitro and in vivo. Here, we summarize the development of TDN and highlight various aspects of TDN applications in cancer therapy based on previous reports, including anticancer drug loading, photodynamic therapy, therapeutic oligonucleotides, bioimaging platforms, and other molecules and discuss a perspective in opportunities and challenges for future TDN-based nanomedicine.


Assuntos
DNA/química , Sistemas de Liberação de Medicamentos , Imagem Molecular , Nanoestruturas , Neoplasias/diagnóstico , Neoplasias/terapia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Portadores de Fármacos , Desenho de Fármacos , Humanos , Imagem Molecular/métodos , Terapia de Alvo Molecular , Nanomedicina/métodos , Nanotecnologia/métodos , Neoplasias/genética , Relação Estrutura-Atividade
17.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188381, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32492470

RESUMO

The United States Food and Drug Administration has permitted number of therapeutic agents for cancer treatment. Most of them are expensive and have some degree of systemic toxicity which makes overbearing in clinical settings. Although advanced research continuously applied in cancer therapeutics, but drug resistance, metastasis, and recurrence remain unanswerable. These accounts to an urgent clinical need to discover natural compounds with precisely safe and highly efficient for the cancer prevention and cancer therapy. Gambogic acid (GA) is the principle bioactive and caged xanthone component, a brownish gamboge resin secreted from the of Garcinia hanburyi tree. This molecule showed a spectrum of biological and clinical benefits against various cancers. In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent. This review also delineates specific molecular mechanism(s) of GA that are involved in anti-cancer, anti-metastasis, anti-angiogenesis, and chemo-/radiation sensitizer activities. Furthermore, recent evidence, development, and implementation of various nanoformulations of gambogic acid (nanomedicine) have been described.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Nanomedicina/métodos , Neoplasias/terapia , Radiossensibilizantes/administração & dosagem , Xantonas/administração & dosagem , Animais , Antineoplásicos Fitogênicos/economia , Quimiorradioterapia/economia , Quimiorradioterapia/métodos , Ensaios Clínicos Fase II como Assunto , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Custos de Medicamentos , Garcinia/química , Humanos , Nanomedicina/economia , Nanopartículas/química , Neoplasias/economia , Radiossensibilizantes/economia , Resinas Vegetais/química , Resultado do Tratamento , Xantonas/economia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Mol Med (Berl) ; 98(6): 789-803, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494931

RESUMO

To date, there is no licensed treatment or approved vaccine to combat the coronavirus disease of 2019 (COVID-19), and the number of new cases and mortality multiplies every day. Therefore, it is essential to develop an effective treatment strategy to control the virus spread and prevent the disease. Here, we summarized the therapeutic approaches that are used to treat this infection. Although it seems that antiviral drugs are effective in improving clinical manifestation, there is no definite treatment protocol. Lymphocytopenia, excessive inflammation, and cytokine storm followed by acute respiratory distress syndrome are still unsolved issues causing the severity of this disease. Therefore, immune response modulation and inflammation management can be considered as an essential step. There is no doubt that more studies are required to clarify immunopathogenesis and immune response; however, new therapeutic approaches including mesenchymal stromal cell and immune cell therapy showed inspiring results.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Vacina BCG/uso terapêutico , Betacoronavirus/genética , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Imunização Passiva/métodos , Imunoterapia Adotiva/métodos , Inibidores de Janus Quinases/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Nanomedicina/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Inibidores de Serino Proteinase/uso terapêutico
19.
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
20.
Nanomedicine (Lond) ; 15(17): 1719-1734, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32462968

RESUMO

Prior research on nanotechnologies in diagnostics, prevention and treatment of coronavirus infections is reviewed. Gold nanoparticles and semiconductor quantum dots in colorimetric and immunochromatographic assays, silica nanoparticles in the polymerase chain reaction and spike protein nanospheres as antigen carriers and adjuvants in vaccine formulations present notable examples in diagnostics and prevention, while uses of nanoparticles in coronavirus infection treatments have been merely sporadic. The current absence of antiviral therapeutics that specifically target human coronaviruses, including SARS-CoV-2, might be largely due to the underuse of nanotechnologies. Elucidating the interface between nanoparticles and coronaviruses is timely, but presents the only route to the rational design of precisely targeted therapeutics for coronavirus infections. Such a fundamental approach is also a viable prophylaxis against future pandemics of this type.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia , Pandemias , Pneumonia Viral , Animais , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Humanos , Camundongos , Nanomedicina/métodos , Nanomedicina/tendências , Nanopartículas/uso terapêutico , Nanotecnologia/métodos , Nanotecnologia/tendências , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia
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