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1.
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
2.
Theranostics ; 10(21): 9591-9600, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863947

RESUMO

Cytokine storms, defined by the dysregulated and excessive production of multiple pro-inflammatory cytokines, are closely associated with the pathology and mortality of several infectious diseases, including coronavirus disease 2019 (COVID-19). Effective therapies are urgently needed to block the development of cytokine storms to improve patient outcomes, but approaches that target individual cytokines may have limited effect due to the number of cytokines involved in this process. Dysfunctional macrophages appear to play an essential role in cytokine storm development, and therapeutic interventions that target these cells may be a more feasible approach than targeting specific cytokines. Nanomedicine-based therapeutics that target macrophages have recently been shown to reduce cytokine production in animal models of diseases that are associated with excessive proinflammatory responses. In this mini-review, we summarize important studies and discuss how macrophage-targeted nanomedicines can be employed to attenuate cytokine storms and their associated pathological effects to improve outcomes in patients with severe infections or other conditions associated with excessive pro-inflammatory responses. We also discuss engineering approaches that can improve nanocarriers targeting efficiency to macrophages, and key issues should be considered before initiating such studies.


Assuntos
Anti-Infecciosos/uso terapêutico , Citocinas/imunologia , Infecções/imunologia , Macrófagos/imunologia , Nanomedicina/tendências , Animais , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Humanos , Infecções/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia
4.
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
5.
Int J Nanomedicine ; 15: 5745-5765, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821099

RESUMO

Glaucoma is a group of diseases characterized by progressive degeneration of retinal ganglion cells, leading to irreversible blindness. Currently, intraocular pressure reduction is the only established treatment available for glaucoma. With this treatment, the progression of the disease can only be delayed and there is no recovery. In addition, the commercially available eye drops have the disadvantage of low compliance and short therapeutic time, while glaucoma surgery always has the risk of failure due to wound fibrosis. Nanotechnology can overcome the limitations of the current treatment through the encapsulation and conjugation of drugs used for lowering intraocular pressure and antifibrotic agents using biodegradable or biocompatible nanoparticles for the sustained release of the drugs to protect the damaged ocular cells. Furthermore, using nanotechnology, treatment can be administered in various forms, including eye drops, contact lens, and ocular inserts, according to the convenience of the patients. Despite the promising results of delaying the progression of glaucoma, the regeneration of damaged ocular cells, including trabecular meshwork and retinal ganglion cells, is another critical hurdle to overcome. Bone marrow-derived mesenchymal stem cells and Müller glia cells can secrete neurogenic factors that trigger the regeneration of associated cells, including trabecular meshwork and retinal ganglion cells. In conclusion, this review highlights the potential therapeutic applications of nanotechnology- and stem cell-based methods that can be employed for the protection and regeneration of ocular cells.


Assuntos
Glaucoma/terapia , Nanomedicina , Animais , Lentes de Contato , Sistemas de Liberação de Medicamentos , Glaucoma/etiologia , Humanos , Nanotecnologia , Malha Trabecular/patologia
6.
Int J Nanomedicine ; 15: 5719-5743, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821098

RESUMO

This review aims to summarize the methods that have been used till today, highlight methods that are currently being developed, and predict the future roadmap for anticancer therapy. In the beginning of this review, established approaches for anticancer therapy, such as conventional chemotherapy, hormonal therapy, monoclonal antibodies, and tyrosine kinase inhibitors are summarized. To counteract the side effects of conventional chemotherapy and to increase limited anticancer efficacy, nanodrug- and stem cell-based therapies have been introduced. However, current level of understanding and strategies of nanodrug and stem cell-based therapies have limitations that make them inadequate for clinical application. Subsequently, this manuscript reviews methods with fewer side effects compared to those of the methods mentioned above which are currently being investigated and are already being applied in the clinic. The newer strategies that are already being clinically applied include cancer immunotherapy, especially T cell-mediated therapy and immune checkpoint inhibitors, and strategies that are gaining attention include the manipulation of the tumor microenvironment or the activation of dendritic cells. Tumor-associated macrophage repolarization is another potential strategy for cancer immunotherapy, a method which activates macrophages to immunologically attack malignant cells. At the end of this review, we discuss combination therapies, which are the future of cancer treatment. Nanoparticle-based anticancer immunotherapies seem to be effective, in that they effectively use nanodrugs to elicit a greater immune response. The combination of these therapies with others, such as photothermal or tumor vaccine therapy, can result in a greater anticancer effect. Thus, the future of anticancer therapy aims to increase the effectiveness of therapy using various therapies in a synergistic combination rather than individually.


Assuntos
Antineoplásicos/farmacologia , Nanomedicina/tendências , Vacinas Anticâncer/imunologia , Humanos , Imunoterapia , Transplante de Células-Tronco , Microambiente Tumoral
8.
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
9.
Int J Nanomedicine ; 15: 4205-4224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606673

RESUMO

Cardiovascular diseases are the number one cause of heart failure and death in the world, and the transplantation of the heart is an effective and viable choice for treatment despite presenting many disadvantages (most notably, transplant heart availability). To overcome this problem, cardiac tissue engineering is considered a promising approach by using implantable artificial blood vessels, injectable gels, and cardiac patches (to name a few) made from biodegradable polymers. Biodegradable polymers are classified into two main categories: natural and synthetic polymers. Natural biodegradable polymers have some distinct advantages such as biodegradability, abundant availability, and renewability but have some significant drawbacks such as rapid degradation, insufficient electrical conductivity, immunological reaction, and poor mechanical properties for cardiac tissue engineering. Synthetic biodegradable polymers have some advantages such as strong mechanical properties, controlled structure, great processing flexibility, and usually no immunological concerns; however, they have some drawbacks such as a lack of cell attachment and possible low biocompatibility. Some applications have combined the best of both and exciting new natural/synthetic composites have been utilized. Recently, the use of nanostructured polymers and polymer nanocomposites has revolutionized the field of cardiac tissue engineering due to their enhanced mechanical, electrical, and surface properties promoting tissue growth. In this review, recent research on the use of biodegradable natural/synthetic nanocomposite polymers in cardiac tissue engineering is presented with forward looking thoughts provided for what is needed for the field to mature.


Assuntos
Materiais Biocompatíveis/química , Coração/fisiologia , Nanocompostos/química , Nanomedicina , Polímeros/química , Engenharia Tecidual/métodos , Animais , Humanos , Nanocompostos/ultraestrutura
10.
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
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.
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
13.
Nat Commun ; 11(1): 3384, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636379

RESUMO

Targeting single mediators has failed to reduce the mortality of sepsis. We developed a telodendrimer (TD) nanotrap (NT) to capture various biomolecules via multivalent, hybrid and synergistic interactions. Here, we report that the immobilization of TD-NTs in size-exclusive hydrogel resins simultaneously adsorbs septic molecules, e.g. lipopolysaccharides (LPS), cytokines and damage- or pathogen-associated molecular patterns (DAMPs/PAMPs) from blood with high efficiency (92-99%). Distinct surface charges displayed on the majority of pro-inflammatory cytokines (negative) and anti-inflammatory cytokines (positive) allow for the selective capture via TD NTs with different charge moieties. The efficacy of NT therapies in murine sepsis is both time-dependent and charge-dependent. The combination of the optimized NT therapy with a moderate antibiotic treatment results in a 100% survival in severe septic mice by controlling both infection and hyperinflammation, whereas survival are only 50-60% with the individual therapies. Cytokine analysis, inflammatory gene activation and tissue histopathology strongly support the survival benefits of treatments.


Assuntos
Dendrímeros/química , Inflamação/terapia , Nanopartículas/química , Sepse/terapia , Adsorção , Animais , Antibacterianos/uso terapêutico , Citocinas/metabolismo , Feminino , Humanos , Hidrogéis , Lipopolissacarídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanomedicina , Padrões Moleculares Associados a Patógenos , Células RAW 264.7
14.
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
15.
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
16.
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
17.
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
19.
ACS Nano ; 14(6): 6383-6406, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32519842

RESUMO

The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of "nanoimmunity by design" can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Betacoronavirus/genética , Betacoronavirus/imunologia , Biomimética , Simulação por Computador , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Desinfecção , Sistemas de Liberação de Medicamentos , Microbiologia Ambiental , Humanos , Imunomodulação , Máscaras , Nanomedicina , Nanotecnologia/tendências , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Fotoquimioterapia , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Vacinas Virais/genética , Vacinas Virais/farmacologia
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